Asked By: Dylan Young Date: created: Jul 10 2024

Why is tibolone not available in the US

Answered By: Jaden Lewis Date: created: Jul 11 2024

Tibolone is banned by WADA as an anabolic steroid category S1 largely due to its conversion to the delta-4 tibolone metabolite, which is a potent androgen.

Asked By: Tyler Davis Date: created: Jul 25 2023

What are the problems with tibolone

Answered By: Jesse Ramirez Date: created: Jul 28 2023

Side-effects of tibolone – Side-effects may include headache, dizziness, nausea, abdominal pain, swollen feet and itching. Breast tenderness is uncommon. Slight bleeding or spotting may commonly occur initially but tends to subside after a few months. Amenorrhoea is achieved by about 80% of women after the first month of treatment with tibolone and over 90% after the third month of therapy (10).

Asked By: Cameron Torres Date: created: Mar 09 2023

Is tibolone safer than HRT

Answered By: Clifford Gray Date: created: Mar 10 2023

Breast cancer – There are limited clinical trial data for breast-cancer risk in healthy women. However, the LIBERATE study in women with previous breast cancer was stopped recently because it was unable to establish non-inferiority of tibolone compared with placebo.

  • The Million Women Study identified a significantly increased risk of having breast cancer diagnosed in tibolone users (relative risk 1·5 ), which is comparable with that for oestrogen-only HRT (1·3 ) and significantly lower than that for combined HRT (2·0 ).
  • Risk increased with longer duration of use and returned to baseline within a few years of stopping treatment.

A study using the General Practice Research Database found no significant increase in risk. Unlike conventional HRT, tibolone has a limited effect on mammographic density.

How many years can you take tibolone?

Key facts –

You’ll usually take tibolone once a day.Tibolone can take up to 3 months to work fully to improve your symptoms.Common side effects include stomach pain, breast tenderness and vaginal irritation but these usually improve in the first few months of treatment.It’s common to take tibolone for 2 to 5 years, and then try stopping to see if your menopause symptoms have improved. If your symptoms last for longer, your doctor can advise on the benefits and risks of continuing to take it.It’s important to see your doctor at least once a year for a check-up and to review whether you need to keep taking tibolone.

Page last reviewed: 5 January 2023 Next review due: 5 January 2026

Why tibolone instead of HRT?

INTRODUCTION – Menopausal symptoms such as hot flushes, affect up to 75% of menopausal women, with ethnicity-induced variations, For most postmenopausal women, the symptoms last for 3–4 years, but may continue for ≥ 10 years in others, Systemic estrogen therapy is the most effective vasomotor symptom treatment and is currently approved by the U.S Food and Drug Administration.

  • Many studies including randomized controlled trials (RCT) have shown that estrogen monotherapy or estrogen and progestogen co-therapy increase the risk of a thromboembolic event,
  • Oral hormone replacement therapy (HRT) increases blood coagulability by increasing clotting factor levels and decreasing antithrombin activity,

Therefore, alternative HRTs are needed for postmenopausal women with high risk factors. Transdermal estrogen is an option absorbed through capillaries in the skin, hence, bypasses the liver and gastrointestinal tract. Compared to oral therapy, it is known to pose a lower risk of thromboembolic events or stroke, owed to its lower influence on C-reactive protein, matrix metalloproteinase-9, and sex hormone-binding globulin,

Thus, it may be safe for postmenopausal women with high risk factors. Additionally, many recent guidelines recommend the use of transdermal HRT in patients with thrombosis or cardiovascular risk factors. Oral tibolone is widely used in many countries such as Europe and Australasia, but not in America.

In the body, it breaks down into three metabolites, which have effects similar to those of both estrogen and progesterone. At the endometrial level, it exerts a tissue-specific progestogenic effect, whereas it has an estrogenic effect on climacteric symptoms and bone,

  • Tibolone is known for its high ability to relieve menopausal and urogenital symptoms and improve bone density, with fewer effects on the endometrium and breasts,
  • In certain cases, due to its ease of administration and induction of less vaginal bleeding and breast tenderness, tibolone is favored over other standard HRTs,

It also has positive effects on sexual well-being and mood, Although several studies have compared the effects of tibolone and oral estrogen on menopausal symptoms, only a few have compared those of tibolone and transdermal estrogen. Thus, this study aimed to compare the effect of tibolone and transdermal estrogen on menopausal symptoms using the menopause rating scale (MRS) questionnaire.

Asked By: Aaron Flores Date: created: Jun 04 2024

What is the difference between tibolone and Livial

Answered By: Alex Ward Date: created: Jun 04 2024

What Livial is used for – Livial tablets contain the active ingredient tibolone, which is a synthetic steroid medicine used for hormone replacement therapy (HRT). It mimics the activity of the female sex hormones in the body. Livial contains tibolone, a substance that has favourable effects on different tissues in the body, such as brain, vagina and bone.

  1. Livial is used in postmenopausal women at least 12 months since their last natural period.
  2. Livial is used for: Relief of symptoms occurring after menopause During the menopause, the amount of estrogen produced by a woman’s body drops.
  3. This can cause symptoms such as hot face, neck and chest (“hot flushes”).

Livial alleviates these symptoms after menopause. You will only be prescribed Livial if your symptoms seriously hinder your daily life. Prevention of osteoporosis After the menopause some women may develop fragile bones (osteoporosis). You should discuss all available options with your doctor.

Asked By: Ethan Allen Date: created: Mar 19 2024

Which is better tibolone or HRT

Answered By: Howard Cox Date: created: Mar 21 2024

Why tibolone is different?, September 2002, Pages 35-39 Tibolone has four features which make it different from conventional hormone replacement therapy. These are: (1) it is a synthetic molecule, (2) it has different activities at different tissues, (3) it is a non-bleeding hormone replacement therapy, (4) it has androgenic activity. Tibolone is a synthetic steroid that is structurally related to the 19 norethisterone derivatives, such as norethynodrel and norethisterone. It is taken in a daily dose orally and after ingestion is metabolised predominantly to three other steroid molecules, δ-4 isomer, 3-α hydroxymetabolite, 3-β hydroxymetabolite. This conversion may occur at the target tissues, therefore, it demonstrates different hormonal activities at different tissues. The δ-4 metabolite predominates at the endometrium demonstrating progestogenic activity resulting in an atrophic endometrium. There is no significant oestrogenic stimulation of the endometrium. One of the main reasons that women commence hormone replacement therapy is that they suffer from the acute symptoms of oestrogen deficiency, and the commonest of these are vasomotor symptoms and urogenital symptoms. Tibolone demonstrates an oestrogenic effect on both these symptoms. Several double-blind placebo controlled studies have demonstrated the drug’s efficacy in alleviating hot flushes, and when directly compared with other compounds, its efficacy was equivalent to those of conjugated oestrogens and oestradiol valerate,, The range in vasomotor symptoms that are experienced in post-menopausal women is vast with some women having one or two hot flushes a week, whereas, some experience seven or eight an hour. If this is occurring during the night and waking them up then this results in significant tiredness and may have an effect on mood. Hot flushes, therefore, are not to be underestimated with regards to their effect on the quality of life in the post-menopausal woman. When ovarian failure occurs, the main urogenital symptoms are vaginal dryness and dyspareunia. Some women also describe urinary frequency which may be secondary to atrophic vaginitis surrounding the urethra. Tibolone has an oestrogenic effect on the vagina, and this has been objectively demonstrated by taking vaginal smears and measuring the karyopyknotic and maturation indices,, In these studies, the objective improvement in the vaginal dryness correlated with subjective improvement of symptoms. In any sexual research, it is difficult to separate out improvement in individual symptoms as improvement of one symptom may produce the domino effect, for example if vaginal dryness is improved this will decrease dyspareunia, which will increase sexual satisfaction, which will increase libido. The other complicating factor with research into sexual symptoms is that an oestrogenic effect on the vagina will improve the biological response, but for sexual behaviour to occur there must be motivational behaviour which is centrally mediated and is probably androgenically driven. Sherwin et al. have demonstrated increased libido and energy levels in post-menopausal women with androgenic replacement therapy. Tibolone has been shown to demonstrate androgenic activity, and Nathorst-Boos and Hammar directly compared the effect of tibolone and continuous combined oestrogen replacement therapy (17-β oestradiol 2 mg plus norethisterone acetate) on sexual activity. They used the Swedish version of McCoy’s sex scale questionnaire at baseline and at 24 and 48 weeks. Both compounds were found to have a positive effect on sexual activity, but tibolone had a greater effect on sexual enjoyment and frequency. This may be due to the androgencity of tibolone. Mood and libido have been shown to be closely linked, and Gennazani et al. demonstrated an improvement in mood in women on tibolone and this correlated with increased levels of β-endorphins. They showed that pre-menopausal women have higher β-endorphin levels than post-menopausal women. A group of post-menopausal women were randomised to tibolone or placebo, the tibolone group showed higher β-endorphin levels equivalent to the pre-menopausal women, whereas, the placebo group’s levels remained low. Their conclusion was that the increase in β-endorphins may improve a post-menopausal woman’s mood. More than 20 years ago Lindsay et al. used single photon absorptiometry to measure the metacarpal bone mineral content in post-menopausal women and they demonstrated that tibolone had a protective effect on bone mass. Modern technology has confirmed this effect using dual energy X-ray absorptiometry (DXA) measuring the clinically relevant sites of the lumbar spine and femur, In this study, 100 women were recruited into an open label study, where 50 women received tibolone 2.5 mg and 50 women no medication. After 1 year, using DXA there was a significant difference between the tibolone and the control group ( P <0.001) in these clinically relevant sites, and this effect has continued long-term, Bone mineral density (BMD) in the lumbar spine and femoral neck increased in the group taking tibolone for 8 years (+4.1 and +4.6%, respectively) and decreased in the untreated group (−7.5 and −6.7%, respectively). The established benefits of taking tibolone for 2–3 years, particularly the prevention of bone loss was, therefore, sustained over an 8-year time period. This bone protective effect has also been demonstrated in older women and Bjarnason et al. have also shown that a lower dose of 1.25 mg is protective. Studies have also been performed in women who have established osteoporosis, and over 2 years tibolone has been shown to have a beneficial effect,, The studies mentioned above were not designed to measure clinical outcome, however, previous analyses indicate this difference is likely to be clinically significant in reducing the risk of fracture, High BMD of either the lumbar spine or femoral neck has been shown to protect the likelihood of any fractures in peri-menopausal women: in one 2-year study of 3222 women, those with a lumbar spine BMD in the lowest quartile of the population had a 2.9-fold greater increased risk of fracture than those in the highest quartile, Long-term tibolone use might, therefore, be expected to lead to fewer fractures than in untreated women. The measurement of biochemical markers of bone turnover has indicated that the effect of tibolone on bone appears to be inhibition of bone resorption and because the markers of bone formation are also suppressed this reflects an overall reduction in bone remodelling. This suggests that tibolone is behaving like an oestrogen on bone. Previously, there was debate as to whether tibolone's effect on bone was due to its androgenic or its oestrogenic activities. In vivo work on oophorectomised rats has now demonstrated that tibolone's effect on bone is oestrogenic. This was demonstrated by randomising rats to tibolone and an anti-oestrogen, tibolone and an anti-androgen, and tibolone and an anti-progestogen, and a placebo. The rats that received the anti-oestrogen lost bone equivalent to the placebo rats, whereas, the rats which received the anti-androgen and the anti-progestogen had equivalent bone preservation to those receiving tibolone, Cardiovascular disease rarely effects women before the menopause, strongly indicating oestrogen deficiency in the aetiology of the disease. Observational studies have shown that HRT decreases coronary heart disease, but the exact mechanism is unclear. The most established effect is on the lipid profile, but the effect on blood flow and endothelial function is undoubtedly important and other factors, for example glucose metabolism clearly play a role. Blood pressure is not significantly altered with tibolone, Tibolone has also been investigated in hypertensive women and was shown to have no deleterious effect on blood pressure in women with established hypertension, Studies of coagulation function have not demonstrated an adverse effect, and in fact there appears to be a tendency towards fibrinolysis. Winkler et al. did a randomised study of 60 post-menopausal women who received tibolone 2.5 mg daily or a continuous combined hormone replacement therapy containing oestradiol (2 mg per day) plus estriol (1 mg) plus norethindrone acetate (1mg per day). The effects on parameters in the clotting cascade were measured at baseline, 12 and 24 weeks of treatment. They demonstrated that tibolone increased fibrinolysis parameters without significantly altering coagulation parameters. The continuous combined hormone replacement therapy resulted in a stimulating effect on parameters of both fibrinolysis and coagulation. With regard to the effect of tibolone on lipids, tibolone causes a decrease in total triglycerides, total cholesterol and high density lipoproteins (HDL) cholesterol, but low density lipoproteins (LDL) are unaffected, This is a different effect from conventional HRT which will decrease total cholesterol, not effect or increase triglycerides and increase HDL. Lipoprotein (a), which is an independent risk factor for coronary heart disease, is significantly reduced with tibolone treatment,, This is interpreted as a positive effect. Although the decrease in HDL may not be interpreted as a beneficial effect, the decrease of triglycerides may be beneficial particularly for diabetic women. Feher et al. investigated the effect of tibolone in a group of insulin dependent diabetics and they found a significant decrease in triglycerides, which is particularly beneficial in non-oestrogen dependent diabetics as triglycerides rather than plasma cholesterol concentrations seem to predict coronary heart disease events. With regard to tibolone and the effect on blood flow, there has been shown to be an increase of peripheral blood flow in the forearm and an increase in blood-flow velocity in nail-bed capillaries, To adequately assess the effect of tibolone on the cardiovascular system we need to look at the hard end points, namely myocardial infarction and cerebovascular accident rates. These data are not yet available. One of the major concerns of HRT administration is the effect on the breast, both in the short- and long-terms. One of the commonest side-effects that women complain of when they commence HRT after not being exposed to oestrogen for some time is breast pain. One randomised controlled trial has shown that after 1 year women on HRT had significantly increased breast pain compared with those on tibolone, This may be a significant advantage of tibolone particularly in women who have not been Tibolone should not be used in peri-menopausal women, as it will increase the incidence of irregular vaginal bleeding. There will not be any adverse effect on the endometrium, but as chaotic bleeding is positively correlated with decreased concordance then this will influence the long-term use of the therapy. Ideally, then tibolone should be restricted for use in post-menopausal women, that is 1 year since their last menstrual period. In women who have been on conventional hormone replacement Tibolone can be used for hormone replacement therapy in post-menopausal women. It is different from conventional hormone replacement therapy because it does not stimulate the endometrium due to the progestogenic dominance at the endometrium. It appears to stimulate the breast tissue less than conventional hormone replacement therapy, and the androgenicity may have the benefit of improving sexual function. The effect on the cardiovascular system compared to conventional hormone replacement

A. Volpe et al. M.H. Milner et al. J. Rymer et al. J. Nathorst-Boos et al. P. Geusens et al. S.R. Cummings et al. U.H. Winkler et al. P. Hardiman et al. W. Haenggi et al. N. Colacurci et al.

P.M. Kicovic et al. Tax L, Goorissen EM, Kicovic PM. Clinical profile of Org OD14. Maturitas 1987;(Suppl. E.P. Morris et al. B. Sherwin et al. Gennazani AR, Benedeck-Jaszman LJ, Hart DM, et al. Effects of Org OD14 on pituitary and β-endorphins in castrated rats.

Propos. – Les données sur le traitement hormonal substitutif (THS) de la ménopause ont été récemment complètement bouleversées. Le but de cette mise au point est de présenter les études les plus récentes sur ce traitement et de décrire les nouvelles alternatives au THS. Actualités et points forts. – En mai 2002 l’étude Women’s Health Initiative (WHI) a été prématurément interrompue du fait d’une augmentation de l’incidence du cancer du sein et de l’infarctus du myocarde dans le groupe traité. Le THS utilisé dans ce bras de l’étude WHI est l’association estrogène conjugué équin + acétate de médroxyprogestérone. Des publications ultérieures ont confirmé que ce type de THS ne peut plus être prescrit dans la prévention primaire de la maladie coronarienne, même si les risques absolus observés étaient bas. Il existe une élévation du risque de maladie veineuse thromboembolique sous THS estroprogestatif. Ce risque ne semble pas exister avec les estrogènes administrés par voie transdermique. Les autres résultats de l’étude WHI ont concerné l’absence de protection du THS vis-à-vis de la démence et du déclin cognitif. Au contraire, les fractures de hanche ostéoporotiques et le cancer du côlon avaient diminué dans le groupe traité. En avril 2004, le bras estrogène seul de cette même étude WHI est également interrompu de façon prématurée devant une augmentation de l’incidence des accidents vasculaires cérébraux. Le risque de cancer du sein est en revanche non majoré dans ce bras après 6,8 ans, posant la question de l’éventuel rôle du progestatif. Perspectives. – Le retentissement de l’étude WHI sur les pratiques cliniques a été majeur. L’agence française de sécurité sanitaire des produits de santé (AFSSAPS) a publié en mai 2004 des recommandations limitant l’indication du THS aux symptômes climatériques invalidants. La durée de prescription doit être la plus courte possible et les doses minimales. La patiente doit être précisément informée des risques encourus et la prescription doit être réévaluée annuellement. Des alternatives hormonales ou non peuvent être proposées comme les phytoestrogènes et la tibolone pour les bouffées de chaleur, et le raloxifène ou les biphosphonates pour la prévention de l’ostéoporose. Dans tous les cas, des habitudes alimentaires saines, l’exercice physique et l’arrêt du tabac seront encouragés. Purpose. – The data concerning post-menopausal hormone replacement therapy (HRT) were recently completely modified. The aim of this review is to present the last studies about post-menopausal HRT and to describe new alternatives to this treatment. Current knowledge and key points. – In May 2002, the women’s health initiative (WHI) trial of post-menopausal HRT was interrupted earlier than expected. The studied hormonal formulation in this arm of the WHI trial was the association of conjugated equine estrogens and medroxyprogesterone. The reason for termination was an increased risk of breast cancer and myocardial infarction in the hormone-therapy group. Later, reports confirmed that this type of HRT could not be used any more for the primary prevention of coronary heart disease even if the absolute risk remained low. There is an increased risk for venous thromboembolism with post-menopausal estroprogestative replacement. This risk does not seem to exist with transdermal estrogens. The other WHI findings concerned the lack of protection against dementia and cognitive decline. On the contrary, osteoporotic hip fractures and colorectal cancers were reduced in the treated group. In April 2004, the estrogen only arm of the same WHI study was also prematurely interrupted because of an increase in the incidence of stroke. The risk of breast cancer was on the contrary not increased after 6.8 years, raising the question of the eventual role of progestins. Perspectives. – The impact of the WHI trial on clinical practice was very important since then. The ” Agence Francaise de sécurité sanitaire des produits de santé ” (AFSSAPS) edited in May 2004 a public recommendation limiting indication for HRT to patients with severe climacteric symptoms. The treatment must now be prescribed for the shortest time and at the minimal dose. The patient has to be precisely informed about the risks with HRT and the practitioner has to re-evaluate his prescription annually. Hormonal or non-hormonal alternatives have also to be considered as phytoestrogens and tibolone for hot flashes, and raloxifene and diphosphonates for osteoporosis prevention. In any case, a healthy diet, exercise and smoking cessation should be encouraged.

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The extracellular matrix (ECM) plays an important role in left ventricular remodeling and progression of heart failure (HF). Biglycan and mimecan are ECM proteins that are abundantly expressed in cardiac tissue but have not been evaluated as prognostic markers in HF. We investigated their interaction with statin treatment and association with adverse outcome in chronic HF. The association between serum levels of biglycan and mimecan and the primary end point (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke), all-cause mortality, CV death, the composite of all-cause mortality/hospitalization for worsening of HF, and the coronary end point was evaluated in 1,390 patients >60 years of age with ischemic systolic HF in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) population, randomly assigned to 10 mg rosuvastatin or placebo. Serum biglycan and mimecan added no prognostic information beyond conventional risk factors, including N-terminal pro–B-type natriuretic peptide. However, statin treatment improved all outcomes except CV death in patients with low biglycan levels (ie, lower tertile), even after full multivariable adjustment. Although circulating levels of mimecan and biglycan were of limited predictive value in patients with chronic HF, circulating biglycan could be a useful marker for targeting statin therapy in patients with HF. The aim of this meta-analysis was to investigate the effects of atorvastatin on serum levels of high-sensitivity C-reactive protein (hs-CRP) and total cholesterol in atrial fibrillation (AF) patients in Asia. By searching English and Chinese language−based electronic databases (ie, PubMed, EBSCO, Ovid, SpringerLink, Wiley, Web of Science, Wanfang database, China National Knowledge Infrastructure, and VIP database), we identified 13 studies relevant to our topic of interest. Data were collected from the 13 studies and analyzed with Comprehensive Meta-Analysis software (version 2.0, Biostat Inc., Englewood, New Jersey). Initially, our database searches retrieved 356 studies (45 in English, 311 in Chinese). Thirteen studies were selected for the meta-analysis following stringent criteria. The data included 1239 patients with AF, of whom 634 were treated with atorvastatin and included in the treatment group, and 605 patients were treated with conventional treatment and included in the control group. The results of our meta-analysis suggested that the serum levels of hs-CRP (mg/L) and total cholesterol (mmol/L) in the treatment group were significantly lower than those of the control group (hs-CRP: standardized mean difference = 0.962; 95% CI, 0.629−1.295, P < 0.001; total cholesterol: standardized mean difference = 1.400; 95% CI, 0.653−2.146, P < 0.001). The findings of this study suggest that atorvastatin may be very effective in decreasing serum levels of hs-CRP and total cholesterol to prevent cardiovascular events. This multicenter, randomized, double-blind, placebo-controlled study assessed the lipid-modifying efficacy/safety profile of anacetrapib 100 mg added to ongoing statin ± other lipid-modifying therapies (LMT) in Japanese patients with heterozygous familial hypercholesterolemia (HeFH). Patients 18–80 years with a genotype-confirmed/clinical diagnosis of HeFH who were on a stable dose of statin ± other LMT for ≥6 weeks and with an LDL-C concentration ≥100 mg/dL were randomized to anacetrapib 100 mg (n = 34) or placebo (n = 34) for 12 weeks, followed by a 12-week off-drug reversal phase. The primary endpoints were percent change from baseline in LDL-C (beta-quantification method ) and safety/tolerability. At Week 12, treatment with anacetrapib reduced LDL-C (BQ) compared to placebo and resulting in a between-group difference of 29.8% (95% CI: −38.6 to −21.0; p < 0.001) favoring anacetrapib. Anacetrapib also reduced non-HDL-C (23.6%; p < 0.001), ApoB (14.1%; p < 0.001) and Lp(a) (48.7%; p < 0.001), and increased HDL-C (110.0%; p < 0.001) and ApoA1 (48.2%; p < 0.001) versus placebo. Anacetrapib 100 mg added to ongoing therapy with statin ± other LMT for 12 weeks was generally well-tolerated. There were no differences between the groups in the proportion of patients who discontinued drug due to an adverse event or abnormalities in liver enzymes, creatinine kinase, blood pressure, electrolytes or adjudicated cardiovascular events. In Japanese patients with HeFH, treatment with anacetrapib 100 mg for 12 weeks resulted in substantial reductions in LDL-C and increases in HDL-C and was well tolerated. ( ) The relationship between tobacco smoke and breast cancer incidence has been studied for many years, but the effect of smoking on hormonal therapy has not been previously reported. We investigated the effect of smoking on hormonal therapy by performing in vitro experiments. We first prepared tobacco smoke condensate (TSC) and examined its effect on estrogen receptor (ER) activity. The ER activity was analyzed using MCF-7-E10 cells into which the estrogen-responsive element (ERE)-green fluorescent protein (GFP) reporter gene had been stably introduced (GFP assay) and performing an ERE-luciferase assay. TSC significantly activated ERs, and upregulated its endogenous target genes. This activation was inhibited by fulvestrant but more weakly by tamoxifen. These results suggest that the activation mechanism may be different from that for estrogen. Furthermore, using E10 estrogen depletion-resistant cells (EDR cells) established as a hormonal therapy-resistant model showing estrogen-independent ER activity, ER activation and induction of ER target genes were significantly higher following TSC treatment than by estradiol (E2). These responses were much higher than those of the parental E10 cells. In addition, the phosphorylation status of signaling factors (ERK1/2, Akt) and ER in the E10-EDR cells treated with TSC increased. The gene expression profile induced by estrogenic effects of TSC was characterized by microarray analysis. The findings suggested that TSC activates ER by both ligand-dependent and -independent mechanisms. Although TSC constituents will be metabolized in vivo, breast cancer tissues might be exposed for a long period along with hormonal therapy. Tobacco smoke may have a possibility to interfere with hormonal therapy for breast cancer, which may have important implications for the management of therapy. High serum concentrations of l -arginine and l -homoarginine increase nitric oxide (NO) availability and thereby improve endothelial function. Information about the association of these markers with peripheral arterial disease (PAD) and related outcomes is sparse. l -arginine, its metabolites and l -homoarginine were analyzed in the CAVASIC Study including 232 male patients diagnosed with intermittent claudication and 246 age- and diabetes-matched controls. After the baseline investigation PAD patients were prospectively followed (median 7 years). The association of these markers with symptomatic PAD at baseline, incident cardiovascular events and all-cause mortality was assessed. At baseline each increase of ln- l -homoarginine and l -arginine by one standard deviation was associated with symptomatic PAD: OR = 0.75, 95%CI 0.59–0.96, P = 0.02 and OR = 1.36, 95%CI 1.07–1.73, P = 0.01, respectively (both models adjusted for ln-CRP, GFR, HDL cholesterol, and current smoking). Only l -arginine remained significant after additional adjustment for ln-NT-proBNP and hs-cTnT: OR = 1.49, P = 0.002. In the Cox regression analysis elevated ln- l -homoarginine significantly reduced the risk to die (n = 38) even independent from ln-NT-proBNP and hs-cTnT: HR = 0.59, 95%CI 0.41–0.84, P = 0.004. l -arginine was significantly predicting incident cardiovascular events (n = 65): HR = 1.68, 95%CI 1.35–2.10, P < 0.001. This study in male patients with intermittent claudication and age- and diabetes-matched controls showed an association of l -homoarginine and l -arginine with PAD. During follow-up, l -arginine was associated with incident cardiovascular events probably due to its primary role in NO metabolism and impact on endothelial integrity. l -homoarginine was related to all-cause mortality implying a broader role in metabolic processes besides endothelial function. Ezetimibe demonstrates decreasing visceral fat and improving insulin sensitivity (IS) in animals and humans. We first reported that simvastatin dose-dependently worsens insulin sensitivity. Whether ezetimibe may compensate untoward effects of simvastatin, depending on dosages of simvastatin has not been investigated in patients with hypercholesterolemia, compared with simvastatin alone. This was a randomized, single-blind, placebo-controlled, parallel study. Fifty-one in each group were given placebo, ezetimibe 10 mg combined with simvastatin 10 mg (Vyto10), ezetimibe 10 mg combined with simvastatin 20 mg (Vyto20), or simvastatin 20 mg alone (Simva20) daily for 2 months. Placebo, Vyto10, Vyto20, and Simva20 improved flow-mediated dilation relative to baseline measurements. Placebo therapy did not significantly change insulin and IS and adiponectin levels and visceral fat area (VFA) and VFA/subcutaneous fat area (SFA) relative to baseline measurements. Vyto10 therapy significantly decreased CRP and insulin levels and increased adiponectin levels and IS, and reduced VFA, VFA/SFA, and blood pressure. Vyto20 therapy did not significantly change insulin levels and IS and adiponectin levels but significantly reduced CRP levels and VFA, VFA/SFA, and blood pressure. Simva20 therapy significantly decreased adiponectin levels and IS but did not significantly change VFA, VFA/SFA, and blood pressure. Of note, these different effects of each therapy were significant by ANOVA. Vyto10, Vyto20, and Simva20 showed significant reduction of LDL cholesterol levels and improvement of flow-mediated dilation in patients with hypercholesterolemia. However, Vyto10, Vyto20, and Simva20 showed significantly differential metabolic effects, depending on dosages of simvastatin.

: Why tibolone is different?

Asked By: Richard Garcia Date: created: Feb 15 2024

Is Livial banned in US

Answered By: Noah Hughes Date: created: Feb 17 2024

US turns away Organon’s Livial US regulators have rejected Organon’s enzyme replacement therapy Livial (tibolone) for the treatment of menopausal symptoms in women, prompting the company – the human healthcare unit of Dutch concern Akzo Nobel – to withdraw its application in the country.

Commenting on the news, Toon Wilderbeek, General Manager of Organon, said: “Although Organon is disappointed with the FDA’s response, we will continue to be committed to this proven brand. Tibolone is available all over the world in countries outside the US where it has been approved and marketed for nearly 20 years.” This is the second setback the drug has suffered this year.

In January, the firm was forced to terminate its LIFT study of Livial – designed to investigate the effect of tibolone on new vertebral fractures in elderly osteoporosis patients – after an interim analysis showed that the drug increased the incidence of stroke.

Organon had hoped that an approval in osteoporosis would inject renewed vigour into Livial, which has seen its sales decline in the face of the general downturn in the HRT market that followed the release of the Women’s Health Initiative study results showing HRT was associated with an increase in cardiovascular risk.

Sales of Livial fell 6% to 164 million euros ($195m) in 2005. : US turns away Organon’s Livial

Asked By: Roger Rodriguez Date: created: May 19 2024

What is the risk of Livial

Answered By: Julian Rivera Date: created: May 20 2024

With use of Livial, the increased risk of ovarian cancer is similar to other types of HRT. There is no evidence that HRT or Livial will prevent a heart attack. Women over the age of 60 who use estrogen-progestogen HRT are slightly more likely to develop heart disease than those not taking any HRT.

Asked By: Fred Sanchez Date: created: Jul 16 2023

What is the safest HRT on the market

Answered By: Evan Cook Date: created: Jul 18 2023

So in summary, the safest types of HRT are the oestrogen applied through the skin as a patch, gel or spray with body identical micronised progesterone. Many women also benefit from testosterone, which may help if you’re forgetful or having trouble concentrating at work.

Asked By: Benjamin Long Date: created: Mar 07 2023

What is the best lowest risk HRT

Answered By: Jaden Rodriguez Date: created: Mar 07 2023

Why is this important? – The results support those found in earlier observational studies. They provide reassurance that HRT is linked to only a small increased risk of breast cancer. The study contradicts a recent analysis, which pooled the results of 58 other studies and found higher than expected risk of breast cancer with HRT.

That study could not make direct comparisons between types of HRT, or different durations of treatment. The current research clarifies the types of HRT with the lowest risk and could guide the HRT of choice for many women. Oestrogen-only HRT has the lowest risk, but can only be taken by women who have had a hysterectomy.

This work supports the current UK guidance around menopause, which says that there is little increased risk of breast cancer with oestrogen-only HRT. Different types of combined HRT had different risks. The lowest was with dydrogesterone, which is not prescribed as often as other progestogens with higher risks (norethisterone, medroxyprogesterone and levonorgestrel).

Can you just stop taking tibolone?

If you stop taking tibolone your menopause symptoms might come back. Talk to your doctor if you’re thinking of stopping. They will help you decide what’s best for you.

Asked By: Stanley Lopez Date: created: Sep 27 2023

When should I stop taking tibolone

Answered By: Dylan Barnes Date: created: Sep 30 2023

You may need to stop taking Tibolone: – If your blood pressure rises – If your skin or the whites of your eyes go yellow (jaundice) – If you suddenly have migraine-type headaches (see section 2 above) – If you have signs of a blood clot (see section 2 above) – If you get any of the problems listed in section 2 (Do not

Can you drink alcohol with tibolone?

Can I consume alcohol with Tibolone? A: Alcohol consumption with this medicine causes an increase in the risk of breast cancer. Avoid alcohol while on this treatment.

Does tibolone cause hair growth?

Are there any side-effects or risks with tibolone? –

Occasionally women report fluid retention and mild weight gain with tibolone- if this occurs it is reasonable to try taking half a tablet (1.25 mg) each day.Vaginal bleeding or spotting may occur in women just after commencing tibolone, however this is uncommon.In large carefully conducted clinical studies tibolone has not been shown to increase the risk of thrombosis (blood clots), heart attack or cancer of the uterus.In contrast to oestrogen and progestin therapy, tibolone does not adversely affect the appearance of mammograms and is not associated with an increased likelihood of breast tenderness.Tibolone may lower the production of a protein that carries thyroid hormone in the blood stream. After starting tibolone women taking thyroid hormone supplements should have their thyriod hormone levels checked after about 6-8 weeks.Tibolone reduces the liver production of a protein called sex hormone binding globulin (SHBG). SHBG binds testosterone so lower SHBG levels means that more testosterone is free in the circulation and can act in cells. For women with low to normal testosterone levels this effect may contribute to enhanced sexual function with tibolone therapy. However, the lowered SHBG may result in androgenic side effects like acne and increased hair growth in a small number of women.Although tibolone is mostly mood enhancing, occasionally women experience depressed mood on tibolone. This is possibly due to it progestogenic effects.In the LIFT study (a study of the use of tibolone to prevent fractures in women over 60 years) an increase in the risk of stroke was reported. This effect is similar to that seen for women who commence oestrogen over the age of approximately 60 years.

Disclaimer: The above information is a general guide and was accurate at the time of production of this page. This information is designed to complement, not replace, the advice of your health professional. : Tibolone

How long can you stay on livial?

What it is used for – Short-term treatment of symptoms resulting from the natural or surgical menopause in post menopausal women. Second line therapy for the prevention of bone mineral density loss in postmenopausal women at high risk of future osteoporotic fractures who are intolerant of, or contraindicated for, other medicinal products approved for the prevention of bone mineral density loss.

After careful selection of users, Livial should be prescribed for the shortest duration consistent with treatment goals. Review the need for continuation of treatment after 6 months, taking into account the risk-benefit ratio for the individual user at the moment (including cardiovascular disease and breast cancer, refer Clinical Trials and Precautions).

Livial should only be continued for as long as the benefit outweighs the risks.

Why don t doctors recommend HRT?

Long-running studies – A lot of what we know about the effects of HRT comes from large studies set up in the early 1990s, a time when HRT was widely prescribed in the US and the UK, not only to relieve menopause symptoms and to prevent osteoporosis, but also to prevent heart disease (as suggested by some, but not all, studies at the time).

  • However, evidence for a beneficial effect of HRT on heart disease risk has not been confirmed.
  • The Women’s Health Initiative (WHI) trials in the US were designed to study cardiovascular risk and the UK Million Women Study ( MWS ) investigated the risk of breast cancer in women using different types of HRT.

Over the last 15 years, these studies, and others, have found little or no evidence that HRT reduces the risk of heart disease. In fact, they have found evidence for an increased risk of blood clots and stroke, They also found an increased risk of breast and ovarian cancer in women using HRT.

Why does tibolone cause weight gain?

Tibolone use decreased serum leptin levels along with tissue fat percentage and total fat mass while inducing a significant increase in body lean mass. Future, larger, and longer follow-up studies will enlighten the impact of HT and Tibolone on leptin levels and weight gain in postmenopausal women.

Asked By: Devin Ward Date: created: Nov 11 2023

Does tibolone improve skin

Answered By: Carter Peterson Date: created: Nov 14 2023

Effects of hormone replacement therapy and tıbolone on skın thıckness and bone ın postmenopausal women To the Editor: This prospective, randomized study was under-taken to investigate the effects of hormone replacement therapy (HRT) and tibolone (T) on skin by ultrasonographic and histologic evaluation and on bone by bone mineral density (BMD).

Forty nonsmoking postmenopausal women were randomized by block randomization to HRT or T. Of the 20 women in the HRT group, one had undergone hysterectomy and received conjugated equine estrogens 0.625 mg daily ( Premarin, Wyeth); 19 women received conjugated equine estrogens 0.625 mg, medroxyprogesterone acetate 5 mg daily continously ( Premelle 5, Wyeth).

The 20 women in the T group received tibolone 2.5 mg daily continuously ( Livial, Organon). Both groups were treated for 12 months. One women in the HRT group and 3 women in the T group did not complete the study. Skin thickness was measured by ultrasonography, three times (at initiation, at 6th and 12th months).

Evaluations were performed at the right thigh 3 c m below the greater trochanter. Skin biopsies were performed two times (at initiation and at 12th month) at the marked location. BMD in the lumbar spine was measured by dual X-ray absorpsiometry (DXA) at initiation and at 12 months. When estimations were done for comparisons within each group using the ANOVA method, 11%±26% (mean±SD) of change could be detected with an α level of,05 and a power of 78%.

The demographic characteristics (age, body mass index, menopause time, gravida, parity) of the two groups were comparable. When evaluated by ultrasonography, a statistically significant increase in skin thickness compared with baseline was observed after 12 months of treatment ( P =0.002) and from 6 to 12 months ( P =0.001) within the HRT group (), but there was no statistically significant changes after the first 6 months compared with baseline ( P =0.68).

In the T group, the increase in skin thickness was statistically significant from baseline to the 6th and 12th months ( P =0.01 and P =0.01)) but not between the 6th and 12th months ( P =0.53). The tibolone group showed a significant increase on the ultrasonographic skin thickness measurement at the 6th month visit compared with the HRT group ( P =0.03).

Histologic skin thickness differences at 12 months were not statistically significant compared with baseline in either the HRT ( P =0.289) or T groups ( P =0.996) (). There were no group differences in the histologic skin thickness measurements ( P =0.29).There were statistically significant changes in T score after 12 months of treatment in the two treatment groups ( P =0.007 in the HRT group, P =0.027 in the T group), but the responses in the two treatment groups were not significantly different from each other ( P =0.269).

Group HRT (n=19) Group T (n=17)
Baseline 1.989 ± 0.395 2.156 ± 0.378
6th month 1.956 ± 0.383 2.340 ± 0.308 * †
12th month 2.222 ±0.407 ‡ 2.393 ± 0.281 †

Baseline and 12 month measurements of skin thickness by skin biopsy and T scores for BMD.

Group HRT (n=19) Group T (n=17)
Skin thickness (mm) BMD (T score) Skin thickness (mm) BMD (T score)
Baseline 3.070±1.134 −1.36 ± 1.02 2.784±1.116 −1.51±1.01
12th month 2.565±1.088 −1.09±0.97 * 2.782±1.239 −1.34±1.07 *

Most studies have measured the thickness of dermis, and dermis is composed virtually entirely of connective tissue. Subcutaneous tissue is an added variable and inclusion of the subcutaneous fat in the measurements results in uncertainty. Therefore in order to obtain good accuracy in the measurements, high frequency ultrasonography has been used to determine skin thickness.

Our study supports these results with the ultrasound technique, a sensitive, reproducible and valid technique for measurement of skin thickness. Dermis thickness in skin biopsy may show wide variations related to how the specimen is cut; if the cut is not perpendicular to the skin surface, the thickness measurement will not be correct.

In concordance with others, significant increases in skin thickness were observed on the sonographic evaluation in our study, but not in the histologic examination in the two treatment groups. Skin and bone changes with estrogen deficiency at the menopause have been shown to be isochronal events.

  1. In our results, both HRT or tibolone therapy was associated with increases in T scores.
  2. Although a small series, our results showed that HRT and tibolone had a benefical effect on skin thickness and on BMD in postmenopausal women.1.
  3. Varila E, Rantala I, Oikarinen A, et al.
  4. The effect of topical oestradiol on skin collagen of postmenopausal women.

Br J Obstet Gynaecol.1995; 105 :985–989.2. Maheux R, Naud F, Rioux M, et al. A randomized, double-blind, placebo-controlled study on the effect of conjugated estrogens on skin thickness. Am J Obstet Gynecol.1994; 170 (2):642–649.3. Brincat M, Kablan S, Studd JWW, et al.

Does tibolone help sleep?

Results: Compared to baseline values, the tibolone group significantly improved on three out of six NHP domains: overall 46.8–25.3, emotional reactions 6.8–2.9 and sleep 19.0–7.2.

Asked By: Jack Peterson Date: created: Feb 01 2024

Is Livial banned in US

Answered By: Ronald Kelly Date: created: Feb 04 2024

US turns away Organon’s Livial US regulators have rejected Organon’s enzyme replacement therapy Livial (tibolone) for the treatment of menopausal symptoms in women, prompting the company – the human healthcare unit of Dutch concern Akzo Nobel – to withdraw its application in the country.

Commenting on the news, Toon Wilderbeek, General Manager of Organon, said: “Although Organon is disappointed with the FDA’s response, we will continue to be committed to this proven brand. Tibolone is available all over the world in countries outside the US where it has been approved and marketed for nearly 20 years.” This is the second setback the drug has suffered this year.

In January, the firm was forced to terminate its LIFT study of Livial – designed to investigate the effect of tibolone on new vertebral fractures in elderly osteoporosis patients – after an interim analysis showed that the drug increased the incidence of stroke.

Organon had hoped that an approval in osteoporosis would inject renewed vigour into Livial, which has seen its sales decline in the face of the general downturn in the HRT market that followed the release of the Women’s Health Initiative study results showing HRT was associated with an increase in cardiovascular risk.

Sales of Livial fell 6% to 164 million euros ($195m) in 2005. : US turns away Organon’s Livial

Which is better tibolone or HRT?

Why tibolone is different?, September 2002, Pages 35-39 Tibolone has four features which make it different from conventional hormone replacement therapy. These are: (1) it is a synthetic molecule, (2) it has different activities at different tissues, (3) it is a non-bleeding hormone replacement therapy, (4) it has androgenic activity. Tibolone is a synthetic steroid that is structurally related to the 19 norethisterone derivatives, such as norethynodrel and norethisterone. It is taken in a daily dose orally and after ingestion is metabolised predominantly to three other steroid molecules, δ-4 isomer, 3-α hydroxymetabolite, 3-β hydroxymetabolite. This conversion may occur at the target tissues, therefore, it demonstrates different hormonal activities at different tissues. The δ-4 metabolite predominates at the endometrium demonstrating progestogenic activity resulting in an atrophic endometrium. There is no significant oestrogenic stimulation of the endometrium. One of the main reasons that women commence hormone replacement therapy is that they suffer from the acute symptoms of oestrogen deficiency, and the commonest of these are vasomotor symptoms and urogenital symptoms. Tibolone demonstrates an oestrogenic effect on both these symptoms. Several double-blind placebo controlled studies have demonstrated the drug’s efficacy in alleviating hot flushes, and when directly compared with other compounds, its efficacy was equivalent to those of conjugated oestrogens and oestradiol valerate,, The range in vasomotor symptoms that are experienced in post-menopausal women is vast with some women having one or two hot flushes a week, whereas, some experience seven or eight an hour. If this is occurring during the night and waking them up then this results in significant tiredness and may have an effect on mood. Hot flushes, therefore, are not to be underestimated with regards to their effect on the quality of life in the post-menopausal woman. When ovarian failure occurs, the main urogenital symptoms are vaginal dryness and dyspareunia. Some women also describe urinary frequency which may be secondary to atrophic vaginitis surrounding the urethra. Tibolone has an oestrogenic effect on the vagina, and this has been objectively demonstrated by taking vaginal smears and measuring the karyopyknotic and maturation indices,, In these studies, the objective improvement in the vaginal dryness correlated with subjective improvement of symptoms. In any sexual research, it is difficult to separate out improvement in individual symptoms as improvement of one symptom may produce the domino effect, for example if vaginal dryness is improved this will decrease dyspareunia, which will increase sexual satisfaction, which will increase libido. The other complicating factor with research into sexual symptoms is that an oestrogenic effect on the vagina will improve the biological response, but for sexual behaviour to occur there must be motivational behaviour which is centrally mediated and is probably androgenically driven. Sherwin et al. have demonstrated increased libido and energy levels in post-menopausal women with androgenic replacement therapy. Tibolone has been shown to demonstrate androgenic activity, and Nathorst-Boos and Hammar directly compared the effect of tibolone and continuous combined oestrogen replacement therapy (17-β oestradiol 2 mg plus norethisterone acetate) on sexual activity. They used the Swedish version of McCoy’s sex scale questionnaire at baseline and at 24 and 48 weeks. Both compounds were found to have a positive effect on sexual activity, but tibolone had a greater effect on sexual enjoyment and frequency. This may be due to the androgencity of tibolone. Mood and libido have been shown to be closely linked, and Gennazani et al. demonstrated an improvement in mood in women on tibolone and this correlated with increased levels of β-endorphins. They showed that pre-menopausal women have higher β-endorphin levels than post-menopausal women. A group of post-menopausal women were randomised to tibolone or placebo, the tibolone group showed higher β-endorphin levels equivalent to the pre-menopausal women, whereas, the placebo group’s levels remained low. Their conclusion was that the increase in β-endorphins may improve a post-menopausal woman’s mood. More than 20 years ago Lindsay et al. used single photon absorptiometry to measure the metacarpal bone mineral content in post-menopausal women and they demonstrated that tibolone had a protective effect on bone mass. Modern technology has confirmed this effect using dual energy X-ray absorptiometry (DXA) measuring the clinically relevant sites of the lumbar spine and femur, In this study, 100 women were recruited into an open label study, where 50 women received tibolone 2.5 mg and 50 women no medication. After 1 year, using DXA there was a significant difference between the tibolone and the control group ( P <0.001) in these clinically relevant sites, and this effect has continued long-term, Bone mineral density (BMD) in the lumbar spine and femoral neck increased in the group taking tibolone for 8 years (+4.1 and +4.6%, respectively) and decreased in the untreated group (−7.5 and −6.7%, respectively). The established benefits of taking tibolone for 2–3 years, particularly the prevention of bone loss was, therefore, sustained over an 8-year time period. This bone protective effect has also been demonstrated in older women and Bjarnason et al. have also shown that a lower dose of 1.25 mg is protective. Studies have also been performed in women who have established osteoporosis, and over 2 years tibolone has been shown to have a beneficial effect,, The studies mentioned above were not designed to measure clinical outcome, however, previous analyses indicate this difference is likely to be clinically significant in reducing the risk of fracture, High BMD of either the lumbar spine or femoral neck has been shown to protect the likelihood of any fractures in peri-menopausal women: in one 2-year study of 3222 women, those with a lumbar spine BMD in the lowest quartile of the population had a 2.9-fold greater increased risk of fracture than those in the highest quartile, Long-term tibolone use might, therefore, be expected to lead to fewer fractures than in untreated women. The measurement of biochemical markers of bone turnover has indicated that the effect of tibolone on bone appears to be inhibition of bone resorption and because the markers of bone formation are also suppressed this reflects an overall reduction in bone remodelling. This suggests that tibolone is behaving like an oestrogen on bone. Previously, there was debate as to whether tibolone's effect on bone was due to its androgenic or its oestrogenic activities. In vivo work on oophorectomised rats has now demonstrated that tibolone's effect on bone is oestrogenic. This was demonstrated by randomising rats to tibolone and an anti-oestrogen, tibolone and an anti-androgen, and tibolone and an anti-progestogen, and a placebo. The rats that received the anti-oestrogen lost bone equivalent to the placebo rats, whereas, the rats which received the anti-androgen and the anti-progestogen had equivalent bone preservation to those receiving tibolone, Cardiovascular disease rarely effects women before the menopause, strongly indicating oestrogen deficiency in the aetiology of the disease. Observational studies have shown that HRT decreases coronary heart disease, but the exact mechanism is unclear. The most established effect is on the lipid profile, but the effect on blood flow and endothelial function is undoubtedly important and other factors, for example glucose metabolism clearly play a role. Blood pressure is not significantly altered with tibolone, Tibolone has also been investigated in hypertensive women and was shown to have no deleterious effect on blood pressure in women with established hypertension, Studies of coagulation function have not demonstrated an adverse effect, and in fact there appears to be a tendency towards fibrinolysis. Winkler et al. did a randomised study of 60 post-menopausal women who received tibolone 2.5 mg daily or a continuous combined hormone replacement therapy containing oestradiol (2 mg per day) plus estriol (1 mg) plus norethindrone acetate (1mg per day). The effects on parameters in the clotting cascade were measured at baseline, 12 and 24 weeks of treatment. They demonstrated that tibolone increased fibrinolysis parameters without significantly altering coagulation parameters. The continuous combined hormone replacement therapy resulted in a stimulating effect on parameters of both fibrinolysis and coagulation. With regard to the effect of tibolone on lipids, tibolone causes a decrease in total triglycerides, total cholesterol and high density lipoproteins (HDL) cholesterol, but low density lipoproteins (LDL) are unaffected, This is a different effect from conventional HRT which will decrease total cholesterol, not effect or increase triglycerides and increase HDL. Lipoprotein (a), which is an independent risk factor for coronary heart disease, is significantly reduced with tibolone treatment,, This is interpreted as a positive effect. Although the decrease in HDL may not be interpreted as a beneficial effect, the decrease of triglycerides may be beneficial particularly for diabetic women. Feher et al. investigated the effect of tibolone in a group of insulin dependent diabetics and they found a significant decrease in triglycerides, which is particularly beneficial in non-oestrogen dependent diabetics as triglycerides rather than plasma cholesterol concentrations seem to predict coronary heart disease events. With regard to tibolone and the effect on blood flow, there has been shown to be an increase of peripheral blood flow in the forearm and an increase in blood-flow velocity in nail-bed capillaries, To adequately assess the effect of tibolone on the cardiovascular system we need to look at the hard end points, namely myocardial infarction and cerebovascular accident rates. These data are not yet available. One of the major concerns of HRT administration is the effect on the breast, both in the short- and long-terms. One of the commonest side-effects that women complain of when they commence HRT after not being exposed to oestrogen for some time is breast pain. One randomised controlled trial has shown that after 1 year women on HRT had significantly increased breast pain compared with those on tibolone, This may be a significant advantage of tibolone particularly in women who have not been Tibolone should not be used in peri-menopausal women, as it will increase the incidence of irregular vaginal bleeding. There will not be any adverse effect on the endometrium, but as chaotic bleeding is positively correlated with decreased concordance then this will influence the long-term use of the therapy. Ideally, then tibolone should be restricted for use in post-menopausal women, that is 1 year since their last menstrual period. In women who have been on conventional hormone replacement Tibolone can be used for hormone replacement therapy in post-menopausal women. It is different from conventional hormone replacement therapy because it does not stimulate the endometrium due to the progestogenic dominance at the endometrium. It appears to stimulate the breast tissue less than conventional hormone replacement therapy, and the androgenicity may have the benefit of improving sexual function. The effect on the cardiovascular system compared to conventional hormone replacement

A. Volpe et al. M.H. Milner et al. J. Rymer et al. J. Nathorst-Boos et al. P. Geusens et al. S.R. Cummings et al. U.H. Winkler et al. P. Hardiman et al. W. Haenggi et al. N. Colacurci et al.

P.M. Kicovic et al. Tax L, Goorissen EM, Kicovic PM. Clinical profile of Org OD14. Maturitas 1987;(Suppl. E.P. Morris et al. B. Sherwin et al. Gennazani AR, Benedeck-Jaszman LJ, Hart DM, et al. Effects of Org OD14 on pituitary and β-endorphins in castrated rats.

Propos. – Les données sur le traitement hormonal substitutif (THS) de la ménopause ont été récemment complètement bouleversées. Le but de cette mise au point est de présenter les études les plus récentes sur ce traitement et de décrire les nouvelles alternatives au THS. Actualités et points forts. – En mai 2002 l’étude Women’s Health Initiative (WHI) a été prématurément interrompue du fait d’une augmentation de l’incidence du cancer du sein et de l’infarctus du myocarde dans le groupe traité. Le THS utilisé dans ce bras de l’étude WHI est l’association estrogène conjugué équin + acétate de médroxyprogestérone. Des publications ultérieures ont confirmé que ce type de THS ne peut plus être prescrit dans la prévention primaire de la maladie coronarienne, même si les risques absolus observés étaient bas. Il existe une élévation du risque de maladie veineuse thromboembolique sous THS estroprogestatif. Ce risque ne semble pas exister avec les estrogènes administrés par voie transdermique. Les autres résultats de l’étude WHI ont concerné l’absence de protection du THS vis-à-vis de la démence et du déclin cognitif. Au contraire, les fractures de hanche ostéoporotiques et le cancer du côlon avaient diminué dans le groupe traité. En avril 2004, le bras estrogène seul de cette même étude WHI est également interrompu de façon prématurée devant une augmentation de l’incidence des accidents vasculaires cérébraux. Le risque de cancer du sein est en revanche non majoré dans ce bras après 6,8 ans, posant la question de l’éventuel rôle du progestatif. Perspectives. – Le retentissement de l’étude WHI sur les pratiques cliniques a été majeur. L’agence française de sécurité sanitaire des produits de santé (AFSSAPS) a publié en mai 2004 des recommandations limitant l’indication du THS aux symptômes climatériques invalidants. La durée de prescription doit être la plus courte possible et les doses minimales. La patiente doit être précisément informée des risques encourus et la prescription doit être réévaluée annuellement. Des alternatives hormonales ou non peuvent être proposées comme les phytoestrogènes et la tibolone pour les bouffées de chaleur, et le raloxifène ou les biphosphonates pour la prévention de l’ostéoporose. Dans tous les cas, des habitudes alimentaires saines, l’exercice physique et l’arrêt du tabac seront encouragés. Purpose. – The data concerning post-menopausal hormone replacement therapy (HRT) were recently completely modified. The aim of this review is to present the last studies about post-menopausal HRT and to describe new alternatives to this treatment. Current knowledge and key points. – In May 2002, the women’s health initiative (WHI) trial of post-menopausal HRT was interrupted earlier than expected. The studied hormonal formulation in this arm of the WHI trial was the association of conjugated equine estrogens and medroxyprogesterone. The reason for termination was an increased risk of breast cancer and myocardial infarction in the hormone-therapy group. Later, reports confirmed that this type of HRT could not be used any more for the primary prevention of coronary heart disease even if the absolute risk remained low. There is an increased risk for venous thromboembolism with post-menopausal estroprogestative replacement. This risk does not seem to exist with transdermal estrogens. The other WHI findings concerned the lack of protection against dementia and cognitive decline. On the contrary, osteoporotic hip fractures and colorectal cancers were reduced in the treated group. In April 2004, the estrogen only arm of the same WHI study was also prematurely interrupted because of an increase in the incidence of stroke. The risk of breast cancer was on the contrary not increased after 6.8 years, raising the question of the eventual role of progestins. Perspectives. – The impact of the WHI trial on clinical practice was very important since then. The ” Agence Francaise de sécurité sanitaire des produits de santé ” (AFSSAPS) edited in May 2004 a public recommendation limiting indication for HRT to patients with severe climacteric symptoms. The treatment must now be prescribed for the shortest time and at the minimal dose. The patient has to be precisely informed about the risks with HRT and the practitioner has to re-evaluate his prescription annually. Hormonal or non-hormonal alternatives have also to be considered as phytoestrogens and tibolone for hot flashes, and raloxifene and diphosphonates for osteoporosis prevention. In any case, a healthy diet, exercise and smoking cessation should be encouraged.

The extracellular matrix (ECM) plays an important role in left ventricular remodeling and progression of heart failure (HF). Biglycan and mimecan are ECM proteins that are abundantly expressed in cardiac tissue but have not been evaluated as prognostic markers in HF. We investigated their interaction with statin treatment and association with adverse outcome in chronic HF. The association between serum levels of biglycan and mimecan and the primary end point (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke), all-cause mortality, CV death, the composite of all-cause mortality/hospitalization for worsening of HF, and the coronary end point was evaluated in 1,390 patients >60 years of age with ischemic systolic HF in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) population, randomly assigned to 10 mg rosuvastatin or placebo. Serum biglycan and mimecan added no prognostic information beyond conventional risk factors, including N-terminal pro–B-type natriuretic peptide. However, statin treatment improved all outcomes except CV death in patients with low biglycan levels (ie, lower tertile), even after full multivariable adjustment. Although circulating levels of mimecan and biglycan were of limited predictive value in patients with chronic HF, circulating biglycan could be a useful marker for targeting statin therapy in patients with HF. The aim of this meta-analysis was to investigate the effects of atorvastatin on serum levels of high-sensitivity C-reactive protein (hs-CRP) and total cholesterol in atrial fibrillation (AF) patients in Asia. By searching English and Chinese language−based electronic databases (ie, PubMed, EBSCO, Ovid, SpringerLink, Wiley, Web of Science, Wanfang database, China National Knowledge Infrastructure, and VIP database), we identified 13 studies relevant to our topic of interest. Data were collected from the 13 studies and analyzed with Comprehensive Meta-Analysis software (version 2.0, Biostat Inc., Englewood, New Jersey). Initially, our database searches retrieved 356 studies (45 in English, 311 in Chinese). Thirteen studies were selected for the meta-analysis following stringent criteria. The data included 1239 patients with AF, of whom 634 were treated with atorvastatin and included in the treatment group, and 605 patients were treated with conventional treatment and included in the control group. The results of our meta-analysis suggested that the serum levels of hs-CRP (mg/L) and total cholesterol (mmol/L) in the treatment group were significantly lower than those of the control group (hs-CRP: standardized mean difference = 0.962; 95% CI, 0.629−1.295, P < 0.001; total cholesterol: standardized mean difference = 1.400; 95% CI, 0.653−2.146, P < 0.001). The findings of this study suggest that atorvastatin may be very effective in decreasing serum levels of hs-CRP and total cholesterol to prevent cardiovascular events. This multicenter, randomized, double-blind, placebo-controlled study assessed the lipid-modifying efficacy/safety profile of anacetrapib 100 mg added to ongoing statin ± other lipid-modifying therapies (LMT) in Japanese patients with heterozygous familial hypercholesterolemia (HeFH). Patients 18–80 years with a genotype-confirmed/clinical diagnosis of HeFH who were on a stable dose of statin ± other LMT for ≥6 weeks and with an LDL-C concentration ≥100 mg/dL were randomized to anacetrapib 100 mg (n = 34) or placebo (n = 34) for 12 weeks, followed by a 12-week off-drug reversal phase. The primary endpoints were percent change from baseline in LDL-C (beta-quantification method ) and safety/tolerability. At Week 12, treatment with anacetrapib reduced LDL-C (BQ) compared to placebo and resulting in a between-group difference of 29.8% (95% CI: −38.6 to −21.0; p < 0.001) favoring anacetrapib. Anacetrapib also reduced non-HDL-C (23.6%; p < 0.001), ApoB (14.1%; p < 0.001) and Lp(a) (48.7%; p < 0.001), and increased HDL-C (110.0%; p < 0.001) and ApoA1 (48.2%; p < 0.001) versus placebo. Anacetrapib 100 mg added to ongoing therapy with statin ± other LMT for 12 weeks was generally well-tolerated. There were no differences between the groups in the proportion of patients who discontinued drug due to an adverse event or abnormalities in liver enzymes, creatinine kinase, blood pressure, electrolytes or adjudicated cardiovascular events. In Japanese patients with HeFH, treatment with anacetrapib 100 mg for 12 weeks resulted in substantial reductions in LDL-C and increases in HDL-C and was well tolerated. ( ) The relationship between tobacco smoke and breast cancer incidence has been studied for many years, but the effect of smoking on hormonal therapy has not been previously reported. We investigated the effect of smoking on hormonal therapy by performing in vitro experiments. We first prepared tobacco smoke condensate (TSC) and examined its effect on estrogen receptor (ER) activity. The ER activity was analyzed using MCF-7-E10 cells into which the estrogen-responsive element (ERE)-green fluorescent protein (GFP) reporter gene had been stably introduced (GFP assay) and performing an ERE-luciferase assay. TSC significantly activated ERs, and upregulated its endogenous target genes. This activation was inhibited by fulvestrant but more weakly by tamoxifen. These results suggest that the activation mechanism may be different from that for estrogen. Furthermore, using E10 estrogen depletion-resistant cells (EDR cells) established as a hormonal therapy-resistant model showing estrogen-independent ER activity, ER activation and induction of ER target genes were significantly higher following TSC treatment than by estradiol (E2). These responses were much higher than those of the parental E10 cells. In addition, the phosphorylation status of signaling factors (ERK1/2, Akt) and ER in the E10-EDR cells treated with TSC increased. The gene expression profile induced by estrogenic effects of TSC was characterized by microarray analysis. The findings suggested that TSC activates ER by both ligand-dependent and -independent mechanisms. Although TSC constituents will be metabolized in vivo, breast cancer tissues might be exposed for a long period along with hormonal therapy. Tobacco smoke may have a possibility to interfere with hormonal therapy for breast cancer, which may have important implications for the management of therapy. High serum concentrations of l -arginine and l -homoarginine increase nitric oxide (NO) availability and thereby improve endothelial function. Information about the association of these markers with peripheral arterial disease (PAD) and related outcomes is sparse. l -arginine, its metabolites and l -homoarginine were analyzed in the CAVASIC Study including 232 male patients diagnosed with intermittent claudication and 246 age- and diabetes-matched controls. After the baseline investigation PAD patients were prospectively followed (median 7 years). The association of these markers with symptomatic PAD at baseline, incident cardiovascular events and all-cause mortality was assessed. At baseline each increase of ln- l -homoarginine and l -arginine by one standard deviation was associated with symptomatic PAD: OR = 0.75, 95%CI 0.59–0.96, P = 0.02 and OR = 1.36, 95%CI 1.07–1.73, P = 0.01, respectively (both models adjusted for ln-CRP, GFR, HDL cholesterol, and current smoking). Only l -arginine remained significant after additional adjustment for ln-NT-proBNP and hs-cTnT: OR = 1.49, P = 0.002. In the Cox regression analysis elevated ln- l -homoarginine significantly reduced the risk to die (n = 38) even independent from ln-NT-proBNP and hs-cTnT: HR = 0.59, 95%CI 0.41–0.84, P = 0.004. l -arginine was significantly predicting incident cardiovascular events (n = 65): HR = 1.68, 95%CI 1.35–2.10, P < 0.001. This study in male patients with intermittent claudication and age- and diabetes-matched controls showed an association of l -homoarginine and l -arginine with PAD. During follow-up, l -arginine was associated with incident cardiovascular events probably due to its primary role in NO metabolism and impact on endothelial integrity. l -homoarginine was related to all-cause mortality implying a broader role in metabolic processes besides endothelial function. Ezetimibe demonstrates decreasing visceral fat and improving insulin sensitivity (IS) in animals and humans. We first reported that simvastatin dose-dependently worsens insulin sensitivity. Whether ezetimibe may compensate untoward effects of simvastatin, depending on dosages of simvastatin has not been investigated in patients with hypercholesterolemia, compared with simvastatin alone. This was a randomized, single-blind, placebo-controlled, parallel study. Fifty-one in each group were given placebo, ezetimibe 10 mg combined with simvastatin 10 mg (Vyto10), ezetimibe 10 mg combined with simvastatin 20 mg (Vyto20), or simvastatin 20 mg alone (Simva20) daily for 2 months. Placebo, Vyto10, Vyto20, and Simva20 improved flow-mediated dilation relative to baseline measurements. Placebo therapy did not significantly change insulin and IS and adiponectin levels and visceral fat area (VFA) and VFA/subcutaneous fat area (SFA) relative to baseline measurements. Vyto10 therapy significantly decreased CRP and insulin levels and increased adiponectin levels and IS, and reduced VFA, VFA/SFA, and blood pressure. Vyto20 therapy did not significantly change insulin levels and IS and adiponectin levels but significantly reduced CRP levels and VFA, VFA/SFA, and blood pressure. Simva20 therapy significantly decreased adiponectin levels and IS but did not significantly change VFA, VFA/SFA, and blood pressure. Of note, these different effects of each therapy were significant by ANOVA. Vyto10, Vyto20, and Simva20 showed significant reduction of LDL cholesterol levels and improvement of flow-mediated dilation in patients with hypercholesterolemia. However, Vyto10, Vyto20, and Simva20 showed significantly differential metabolic effects, depending on dosages of simvastatin.

: Why tibolone is different?

Asked By: Ryan Cox Date: created: Jul 12 2023

Is tibolone FDA approved

Answered By: Robert Diaz Date: created: Jul 12 2023

Generic Name Tibolone DrugBank Accession Number DB09070 Background Tibolone is a synthetic steroid hormone drug, which is mainly non-selective in its binding profile, acting as an agonist primarily at estrogen receptors (ER), with a preference for ER alpha 11,

  • Tibolone (Livial, Org OD 14), produced by Organon (West Orange, NJ), is a synthetic steroid that possesses estrogenic, androgenic and progestogenic properties.
  • It has been used in Europe for almost 2 decades, primarily for the prevention of postmenopausal osteoporosis and the treatment of post-menopausal symptoms 4,

Tibolone is approved in 90 countries to manage menopausal symptoms and in 45 countries to prevent the development of osteoporosis 12, In June 2006, Organon Pharmaceuticals announced the receipt of a Not Approvable Letter from the U.S. Food and Drug Administration (FDA), advising the company that the New Drug Application (NDA) for tibolone had not been approved 5, Weight Average: 312.453 Monoisotopic: 312.208930142 Chemical Formula C 21 H 28 O 2 Synonyms

17-hydroxy-7alpha-methyl-19-nor-17alpha-pregn-5(10)-en-20-yn-3-onetibolonaTibolonetibolonum

External IDs

ORG OD 14

Indication For the relief of post-menopausal symptoms and for the prevention of osteoporosis 7, Reduce drug development failure rates Build, train, & validate machine-learning models with evidence-based and structured datasets. Build, train, & validate predictive machine-learning models with structured datasets. Associated Conditions

Vasomotor Symptoms Associated With Menopause

Contraindications & Blackbox Warnings Avoid life-threatening adverse drug events Improve clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more. Avoid life-threatening adverse drug events & improve clinical decision support.

  1. Pharmacodynamics Tibolone prevents bone loss and treating post-menopausal symptoms without stimulating the endometrial tissues, which may lead to malignancy.
  2. Typical, drugs that treat post-menopausal symptoms such as estrogen, have a proliferative effect on the endometrium, increasing the risk of endometrial carcinoma 8,

The effects on the bone, brain and vaginal tissues can be explained by the estrogenic activity of tibolone. It is important to note that activity is not expressed in the endometrium. Tibolone behaves differently from estrogen plus progesterone combinations on the breast.

  • Therefore, tibolone can be characterized as a selective estrogen activity regulator 1,
  • Tibolone has been demonstrated to be an effective agent in treating symptoms associated with menopause.
  • A 16 week trial in 1189 women examined the effect of tibolone 2.5 mg once daily on climacteric symptoms.
  • Women treated with tibolone showed improvement from baseline in typical menopausal symptoms including hot flashes, sweating, insomnia, and anxiety 14,

Mechanism of action This drug’s effects are owed to the activity of its metabolites in various tissues 4, Upon ingestion, tibolone is quickly converted into three major metabolites: 3 alpha- and 3 beta-hydroxy-tibolone, which have oestrogenic effects, and the Delta(4)-isomer, which has progestogenic and androgenic effects.

The specific tissue-selective effects of tibolone occur due to the metabolism, regulation of enzymes and receptor activation that varies in different tissues of the body. The bone-conserving effects occur due to estradiol receptor activation, while the progesterone and androgen receptors are not involved in this process.

Breast tissue of monkeys is not found to be stimulated after tibolone administration, as occurs with estrogen plus progesterone used in combination. This is explained by the fact that tibolone and its metabolites inhibit sulphatase and 17 beta-hydroxysteroid dehydrogenase (HSD) type I and stimulate sulphotransferase and 17 beta-HSD type II,

  1. The combined effects of this process prevent the conversion to active estrogens.
  2. In the uterus, the progestogenic activity of the Delta(4)-metabolite and the effect on estrogen-inactivating enzymes prevent estrogenic stimulation.
  3. The mammary gland is not stimulated in currently used animal models.
  4. Tibolone has been shown to regulate estrogenic activity in several tissue types by influencing the availability of estrogenic compounds for the estradiol receptor in a selective manner 2,

Additionally, tibolone modulates cellular homeostasis in the breast by preventing breast tissue proliferation and stimulating cell apoptosis. Tibolone does not stimulate the endometrium because of the action of its highly stable progestogenic metabolite (Delta(4)-isomer) in combination with an effect on the sulfatase (inhibition)-sulfotransferase (stimulation) system.

The estrogenic metabolites of tibolone have direct, favorable effects on the cardiovascular system and, in animal models, this drug has shown no adverse consequences. The tissue-selective effects of tibolone are the result of metabolism, enzyme regulation and receptor activation that vary in different tissues.

The bone-preserving effects of tibolone are the result of estradiol receptor activation, while other steroid receptors, mainly the progesterone and androgen receptors, are not involved in this process. In a study of monkeys, breast tissue was not stimulated, which occurs with estrogen and progesterone, because tibolone and its metabolites inhibit sulfatase and 17 beta-hydroxysteroid _dehydrogenase (HSD) type I and stimulate _sulfotransferase and 17 beta-HSD type II,

The simultaneous effects of this process halt conversion to active estrogens. Additionally, tibolone affects cellular homeostasis in the breast by preventing proliferation and stimulating apoptosis. Tibolone does not stimulate the endometrium due to the action of the highly stable progestogenic metabolite (Delta(4)-isomer) in combination with an effect on the sulphatase (inhibition)-sulphotransferase (stimulation) pathway 1,

The levels of tibolone metabolites and the alteration of hormonal activities vary according to the tissue type. In endometrial tissue the Δ4-isomer functions as a progestagen, however, in the brain and liver, it shows androgenic effects. In breast tissue, the primary actions of tibolone are strong inhibition of sulfatase activity and weak inhibition of 17β-hydroxysteroid dehydrogenase activity, which leads to blocking the conversion estrone sulfate to E2 4,

Target Actions Organism
A Estrogen receptor alpha antagonist agonist Humans

Absorption Tibolone is extensively and rapidly absorbed after oral administration 14, The parent drug undergoes extensive metabolism, with. Greater than 80% of a radioactive dose excreted from the body as metabolites, which suggests very low plasma concentrations of tibolone.

  • Plasma concentrations of the metabolites appear within 30 minutes and peak within 1–1.5 hours.2,7 The plasma concentrations of the hydroxymetabolites are higher than those of the ∆4-isomer.
  • Food does not appear to have an effect on the absorption of this drug 14,
  • Volume of distribution Not Available Protein binding Tibolone is 96% bound to plasma proteins, most likely albumin.16 Metabolism Tibolone is metabolized mainly in the liver 4,

The cytochrome P450 isoenzyme system is involved in minor hydroxylation of tibolone 14, Tibolone is rapidly converted into three major metabolites: 3 alpha- and 3 beta-hydroxy-tibolone, which have oestrogenic effects, and the Delta(4)-isomer, which has both progestogenic and androgenic effects.

The 3-hydroxy metabolites are present in the circulation, predominantly in their inactive sulfated form 1, Route of elimination Excreted in the urine and feces in the form of sulfated metabolites.4, 14 About 40% of the drug is excreted as metabolites in urine.16 The predominant route of elimination of tibolone is via the feces: 14 about 60% of the drug is excreted as metabolites in feces.16 Half-life The elimination half-life is approximately 45 h 4,

Clearance Elimination of tibolone is not dependent renal function 14, Adverse Effects Improve decision support & research outcomes With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. Improve decision support & research outcomes with our structured adverse effects data. Toxicity >2000 mg/kg MSDS The Million Women Study (MWS), which had a prospective observational design, studied the use of hormone replacement therapy. The results indicated that the increase in the incidence of breast cancer with estrogen and progestogen (compared to estrogen alone) was greater than the reduction in occurrence of endometrial cancer associated with adding progestogen to estrogen therapy. The MWS also reported a marked increase in the incidence of breast cancer with tibolone and with implanted and transdermal estrogen-only preparations 6, Tibolone treatment in rodent studies showed an increased association with the development of a range of tumors in long-term oral carcinogenicity studies. These tumors included pituitary adenomas, mammary carcinomas and fibroadenomas, hepatic adenomas, uterine carcinoma, stromal polyps and stromal sarcoma, and carcinomas of the urinary bladder and testes. Tibolone failed to show any evidence of genotoxicity in studies for gene mutations, chromosomal damage as well as DNA damage 9, Other adverse effects these include dizziness, headache, nausea, abdominal pain, rashes, pruritus, weight gain, edema, and migraine 16, Pathways Not Available Pharmacogenomic Effects/ADRs Not Available Drug Interactions This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Approved Vet approved Nutraceutical Illicit Withdrawn Investigational Experimental All Drugs

Drug Interaction
Integrate drug-drug interactions in your software
Abciximab Tibolone may increase the anticoagulant activities of Abciximab.
Aceclofenac Aceclofenac may increase the thrombogenic activities of Tibolone.
Acenocoumarol Tibolone may increase the anticoagulant activities of Acenocoumarol.
Acetohexamide The therapeutic efficacy of Acetohexamide can be decreased when used in combination with Tibolone.
Adalimumab Tibolone may increase the thrombogenic activities of Adalimumab.
Aducanumab Tibolone may increase the thrombogenic activities of Aducanumab.
Alemtuzumab Tibolone may increase the thrombogenic activities of Alemtuzumab.
Alirocumab Tibolone may increase the thrombogenic activities of Alirocumab.
Alteplase Tibolone may increase the anticoagulant activities of Alteplase.
Amitriptyline The serum concentration of Amitriptyline can be increased when it is combined with Tibolone.

Food Interactions

Avoid St. John’s Wort. St. John’s Wort induces CYP3A4, increasing the metabolism of estrogens and progesterone and therefore reducing the efficacy of tibolone. Take with or without food.

UNII FF9X0205V2 CAS number 5630-53-5 InChI Key WZDGZWOAQTVYBX-XOINTXKNSA-N InChI InChI=1S/C21H28O2/c1-4-21(23)10-8-18-19-13(2)11-14-12-15(22)5-6-16(14)17(19)7-9-20(18,21)3/h1,13,17-19,23H,5-12H2,2-3H3/t13-,17-,18+,19-,20+,21+/m1/s1 IUPAC Name (1S,9R,10R,11S,14R,15S)-14-ethynyl-14-hydroxy-9,15-dimethyltetracycloheptadec-2(7)-en-5-one SMILES 12CC(O)(C#C)1(C)CC1()C3=C(CC(=O)CC3)C()(C)21

Is there a shortage of Livial?

This information is provided to the BMS by the pharmaceutical companies. – Besins Healthcare (UK) Ltd HRT products DIMETRUM (dienogest) 2mg tablet. This product is in stock IMVAGGIS (estriol) 0.03mg pessary. We are regrettably experiencing an interruption to supplies.

  • Our next delivery is delayed and we are now expecting it mid-July 2023.
  • We sincerely regret any inconvenience this may cause.
  • OESTROGEL (estradiol (0.06% w/w)) Pump-pack This product is in stock.
  • Note there are two pack shapes now available in the UK.
  • One is a conical shaped bottle with a blue lid and the other is a cylindrical bottle with a white lid.

It is only the pack that is different and the formulation of the product remains the same. TESTOGEL (testosterone) 50mg gel in sachets. This product is no longer supplied in the UK. TESTOGEL (testosterone) 40.5mg gel in sachets. This product is in stock.

  • TESTOGEL (testosterone) 16.2mg/g gel.
  • This product is in stock.
  • UTROGESTAN (micronised progesterone) 100mg capsules We received significant supplies of Utrogestan 100mg last week (week commencing 23 June) which has been made available to wholesalers.
  • We expect more supplies to arrive this week (week commencing 3 July) and the coming weeks which we expect to help ease the supply situation.

If you are a patient, please check with your pharmacy and in case of any concerns about your treatment please consult your GP for advice. UTROGESTAN VAGINAL (micronised progesterone) 200mg capsules This product is in stock, Gedeon Richter Gedeon Richter is the Marketing Authorisation holder of the following products.

  • Lenzetto 1.53 mg/spray, transdermal spray, solution, MA number PL 04854/0130.
  • Lenzetto is available in the UK, in x1 and x3 packs.
  • Vagirux 10 micrograms vaginal tablets, MA number PL04854/0184 Our current delivery schedules for our HRT products are anticipated to meet fully the expected future market demands,

Orion HRT products We continue receiving frequent supplies of all HRT products from our European parent company. We are doing everything possible to increase supplies further for the UK and now have a strong supply for all strengths of Sandrena Gel. We are currently out of stock of Indivina 1mg x 2.5mg until Q3 but fully stocked with all other strengths of Indivina.

Product Availability
Bijuve (estradiol/progesterone) Available – Fully in stock
Evorel
Evorel ® Conti (estradiol/norethisterone) Available – Fully in stock
Evorel ® Sequi (estradiol/norethisterone) Available – Fully in stock
Evorel ® 25 (estradiol) Available – Fully in stock
Evorel ® 50 (estradiol) Available – Fully in stock
Evorel ® 75 (estradiol) Available – Fully in stock
Evorel ® 100 (estradiol) Available – Fully in stock
FemSeven
FemSeven ® Conti (estradiol/levonorgestrel) Available – Fully in stock
FemSeven ® Sequi (estradiol/levonorgestrel) Expected Q1 2024
FemSeven ® 50 (estradiol) Available – Fully in stock
FemSeven ® 75 (estradiol) Unavailable
FemSeven ® 100 (estradiol) Unavailable
Intrarosa ® (Prasterone) Available – Fully in stock
Zoely ® (nomegestrol acetate/estradiol) Available – Fully in stock

We are currently experiencing a shortage of FemSeven® 75 and FemSeven® 100 in the UK Marketplace. To deal with this shortage, we have substantially increased our manufacture and are expecting new stock will be available by October 2023. Theramex will continue to keep health care professionals informed of any changes.

We would like to thank both patients and prescribers for their continued patience. Note to pharmacists For pharmacists and healthcare professionals who wish to place orders, please contact Alliance Healthcare via your usual channels. Novartis pharmaceuticals ESTRADOT TTS-50 – Available ESTRADOT TTS-25 – Available ESTRADOT TTS-37.5 – Available ESTRADOT TTS-100 – Available We continue to see increased demand,

Norgine UK – Estraderm MX patches

ESTRADERM MX100 1X24 PATCH GB – in stockESTRADERM MX100 1X8 PATCH GB – in stockESTRADERM MX25 1X24 PATCH GB – in stockESTRADERM MX25 1X8 PATCH GB – in stockESTRADERM MX50 1X24 PATCH GB – in stockESTRADERM MX50 1X8 PATCH GB – in stockESTRADERM MX75 1X24 PATCH GB- in stockESTRADERM MX75 1X8 PATCH GB – in stock

Viatris UK Healthcare (previously Mylan) Viatris HRT stock can be obtained through AAH, Alliance and Phoenix, if you need assistance from us please contact [email protected], Femoston ® Range – all available • Femoston ® 1mg estradiol + 10mg dydrogesterone.

Available • Femoston ® 2mg estradiol + 10mg dydrogesterone. Available • Femoston ® -conti 1mg estradiol + 5mg dydrogesterone. Available • Femoston ® -conti ultra-low dose 0.5mg estradiol + 2.5mg dydrogesterone. Available Zumenon ® Range – all available • Zumenon ® 1mg estradiol. Available • Zumenon ® 2mg estradiol.

Available Elleste™ oral Range – all available • Elleste Solo™ 1mg estradiol. Available • Elleste Solo™ 2mg estradiol. Available • Elleste Duet™ 1mg estradiol + 1mg norethisterone acetate. Available • Elleste Duet™ 2mg estradiol + 1mg norethisterone acetate.

Available • Elleste Duet™ Conti 2mg estradiol + 1mg norethisterone acetate. Available Pfizer We have no supply issues with our HRT products. We had some supply constraints with Estring but through careful stock management we have managed to avoid an out of stock situation with this product and maintained consistent supply for patients Novo Nordisk HRT products No shortage of supplies of any of their HRT products: Kliovance 1mg estradiol + 0.5mg norethisterone acetate.

Available Kliofem 2mg estradiol + 1mg norethisterone acetate. Available Novofem 1 mg estradiol + 1 mg norethisterone acetate. Available Trisequens 2mg/2mg/1mg estradiol + 1mg norethisterone acetate. Available Vagifem 10mcg topical vaginal oestrogen. Available If difficulty obtaining supplies, the company suggested contacting their customer care on: [email protected]; or telephone 0800 023 2573., to guide them to their wholesale suppliers.

  • Bayer Progynova 1mg estradiol tablets.
  • Available Progynova 2 mg estradiol tablets.
  • Available Progynova TS estradiol 50 patches.
  • Available Progynova TS estradiol 100 patches.
  • Out of stock now, next delivery expected on 28 Oct 2023 Please be informed that we have sufficient stock of MIRENA I.U.
  • WITH NEW INSERTER (pip code 2744985) and do not have shortage forecast as of now.

Qlaira is in stock through our wholesale suppliers, AAH and Phoenix. Aspen Ovestin. Estriol topical vaginal cream. Available Marlborough Estriol 0.01%. Topical Estriol vaginal cream. Available Consilient Health UK Ltd Blissel 50 micrograms estriol vaginal gel.

Available Shionogi BV Senshio (ospemifene) 60mg 28 tablet pack – Available Shionogi UK has decided to discontinue commercial support behind Senshio (ospemifene). However, Shionogi Europe will continue to support existing and upcoming formulary applications through the EU Med Affairs and Senshio remains available to prescribe in the UK for patients who need it.

Any supply issues, medical information enquiries or questions regarding formulary applications should be addressed to the company on 020 3053 4190 or [email protected] Kyowa Kirin Ltd Kyowa Kirin International can confirm that we are currently experiencing supply delays impacting availability of Tostran 2% gel, a product used in replacement therapy for male hypogonadism when testosterone deficiency has been confirmed.

We take this situation very seriously and are doing our utmost to restore stock to normal levels as soon as possible. We encourage any patients who are currently using Tostran 2% gel to speak to their treating physician if they have any questions or concerns. In the meantime, Kyowa Kirin is in discussion with all relevant parties, including regulatory agencies and manufacturers.

Lawley Pharmaceuticals AndroFeme 1 testosterone 1% cream (Specials unlicensed supply). Available AndroFeme 1 remains available in the UK with no shortages anticipated and the UK ‘specials’ status remains. On 23rd November 2020, Australia’s regulatory authority granted AndroFeme 1 full marketing authorisation and registration on the Australian Register of Therapeutic Goods.

  1. The approved indication is: the management of hypoactive sexual desire dysfunction (HSDD) in postmenopausal women.
  2. On 24 th February 2023, a Marketing Authorisation Application (MAA) for AndroFeme was submitted to the UK MHRA.
  3. This application was validated and accepted for assessment on 16 th March 2023.

Androlabs (part of the Simple Pharma group) Testavan 2% testosterone gel. Testavan is in good supply across the UK and Europe, with no shortages anticipated.23mg per pump actuation. Off-label use for female testosterone replacement. Each pack of Testavan comes with a patented “hands-free” applicator which minimises secondary transfer risk.

  1. Androlabs is a UK headquartered company and is available for contact at [email protected],
  2. Please get in contact if there are any access problems – Testavan is not yet available in every formulary in the UK.
  3. Organon Pharma (UK) Ltd We can confirm there is no change in the supply for Livial.
  4. Both pack sizes are available, and we continue to meet demand for UK product in full.

Livial (2.5 mg Tibolone) (x84 packs). Available Livial (2.5 mg Tibolone) (x28 packs). Available GPs and Pharmacists should be able to provide guidance on suitable alternatives. Paula Briggs, Chairman, British Menopause Society