Tibolone is a synthetic steroid taken as a daily tablet to treat menopausal symptoms and, in some countries, to prevent osteoporosis. It is sold mainly as Livial (Organon). It is unusual because it is a “prodrug” (a compound the body converts into active forms): its metabolites act on estrogen, progesterone and androgen receptors, depending on the tissue.
The most important fact: tibolone is a women’s-health drug with a mixed safety record, not a muscle-building agent. In large randomized trials it reduced fractures and hot flushes, but it raised the risk of stroke in older women and the risk of breast cancer returning in women who had had breast cancer. It is approved in the UK and many other countries, it is not available in the United States, and WADA lists it as an anabolic androgenic steroid.
This page summarizes what the UK product label, the randomized trials and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Synthetic 19-nor steroid with estrogenic, progestogenic and androgenic metabolites |
| Brand | Livial 2.5 mg tablets (Organon); first UK authorisation March 1991 |
| Route | Oral tablet |
| Labeled dose (UK) | 2.5 mg once daily; 1.25 mg was used in the LIFT fracture trial |
| Approved uses (UK) | Menopausal (estrogen-deficiency) symptoms; osteoporosis prevention in high-risk women who cannot use other drugs |
| Half-life (label) | Parent drug too low to measure; 3α-OH metabolite ≈ 5.8 h after one dose and ≈ 7.7 h at steady state |
| US status | Not available in the US; not named in the DEA anabolic steroid schedule |
| WADA status | Prohibited at all times (S1.1 anabolic androgenic steroids) |
What it is
Tibolone’s chemical name is 17-hydroxy-7α-methyl-19-nor-17α-pregn-5(10)-en-20-yn-3-one: formula C₂₁H₂₈O₂, molecular weight 312.4 g/mol, CAS 5630-53-5. Its development code was Org OD14 (PubChem CID 444008). As the “19-nor” in its name shows, it lacks the carbon-19 methyl group, like nandrolone, but it is a distinct molecule with its own metabolites.
Tibolone itself does little. After a dose it is quickly converted into three active compounds (Livial SmPC; Kloosterboer, J Steroid Biochem Mol Biol 2001):
| Metabolite | Receptor activity | Main effect |
|---|---|---|
| 3α-hydroxy-tibolone | Estrogen receptor only | Relieves hot flushes and vaginal dryness; protects bone |
| 3β-hydroxy-tibolone | Estrogen receptor only | Same as above |
| Δ4-isomer | Progesterone and androgen receptors | Progestogen effect on the uterine lining; androgen-like effects |
The manufacturer’s researchers described this as “tissue-specific” action. In their account, the Δ4-isomer formed locally in the uterus keeps the lining from being stimulated, and in breast cell lines tibolone strongly inhibited sulfatase, an enzyme that releases active estrogen (Kloosterboer, J Steroid Biochem Mol Biol 2001). Much of that work was done in cell lines and animals. The breast-cancer recurrence result in the LIBERATE trial (below) shows that the tissue-selective model did not protect the breast in women with a history of breast cancer.
Tibolone also lowers sex hormone-binding globulin (SHBG), the protein that carries testosterone in the blood. In a 6-month randomized trial in 166 postmenopausal women, tibolone 2.5 mg cut SHBG by 50% and raised circulating androgens, while it barely changed estrogen levels (Hofling et al., Gynecol Endocrinol 2005). Lower SHBG means more of the testosterone in blood is free (unbound), which adds to tibolone’s androgenic profile.
Pharmacokinetics
Tibolone is absorbed rapidly and extensively, and food does not change how much is absorbed. Because it is metabolized so fast, blood levels of tibolone and of the Δ4-isomer are very low. Most of the drug leaves the body as sulfated metabolites, mainly in the feces, and renal function does not change the kinetics (Livial SmPC).
Label values for a 2.5 mg dose:
| Parameter | Tibolone | 3α-OH metabolite | 3β-OH metabolite | Δ4-isomer |
|---|---|---|---|---|
| Peak level, single dose | 1.37 ng/mL | 14.23 ng/mL | 3.43 ng/mL | 0.47 ng/mL |
| Time to peak, single dose | 1.08 h | 1.21 h | 1.37 h | 1.64 h |
| Half-life, single dose | Not determined | 5.78 h | 5.87 h | Not determined |
| Half-life, repeated dosing | Not determined | 7.71 h | Not determined | Not determined |
In a crossover study of single 1.25 mg and 2.5 mg doses, age (45–55 vs 65–75 years) did not significantly change peak levels, time to peak or half-life of tibolone and its metabolites. The two tablet strengths gave equivalent total exposure (Timmer et al., Br J Clin Pharmacol 2002).
Approved medical use
The UK label lists two indications (Livial SmPC):
- treatment of estrogen-deficiency symptoms in women more than one year after menopause;
- prevention of osteoporosis in postmenopausal women at high risk of fracture who cannot take, or should not take, other osteoporosis drugs.
Key labeling points:
- Dose: one 2.5 mg tablet daily, at the lowest effective dose for the shortest time for menopausal symptoms. A separate progestogen should not be added.
- Timing: start at least 12 months after the last natural period (immediately after surgical menopause).
- Stroke: the decision to prescribe should consider stroke risk, particularly in women over 60.
- Review: benefits and risks should be reassessed at least once a year.
In 2008 the LIFT investigators reported that tibolone was approved in 90 countries for menopausal symptoms and in 45 for osteoporosis prevention (Cummings et al., NEJM 2008). It is not available in the United States (Morga et al., Menopause 2024).
What the research shows
Hot flushes and bleeding
A 2016 Cochrane review pooled 46 randomized trials with 19,976 women (Formoso et al., Cochrane 2016):
| Comparison | Outcome | Result |
|---|---|---|
| Tibolone vs placebo | Hot flushes and night sweats | Better with tibolone: SMD −0.99 (95% CI −1.10 to −0.89; 7 trials, 1,657 women) |
| Tibolone vs placebo | Unscheduled bleeding | More with tibolone: OR 2.79 (95% CI 2.10–3.70); about 31–44% vs 18% |
| Tibolone vs combined HT | Hot flushes and night sweats | Combined estrogen-progestin therapy worked slightly better (OR 1.36, 95% CI 1.11–1.66) |
| Tibolone vs combined HT | Unscheduled bleeding | Less with tibolone: OR 0.32 (95% CI 0.24–0.41); about 18–27% vs 47% |
The reviewers rated this evidence moderate quality. When trials at high risk of attrition bias were removed, the benefit over placebo shrank (SMD −0.61). Most trials were funded by manufacturers or did not disclose funding.
Fractures: the LIFT trial
The Long-Term Intervention on Fractures with Tibolone (LIFT) trial randomized 4,538 women aged 60–85 with osteoporosis to tibolone 1.25 mg daily or placebo (Cummings et al., NEJM 2008). It was stopped in February 2006, after a median of 34 months, because of an excess of strokes.
| Outcome | Tibolone vs placebo | Relative hazard (95% CI) |
|---|---|---|
| Vertebral fracture | 70 vs 126 per 1,000 person-years | 0.55 (0.41–0.74) |
| Nonvertebral fracture | 122 vs 166 per 1,000 person-years | 0.74 (0.58–0.93) |
| Invasive breast cancer | Fewer cases | 0.32 (0.13–0.80) |
| Colon cancer | Fewer cases | 0.31 (0.10–0.96) |
| Stroke | More cases | 2.19 (1.14–4.23) |
| Coronary heart disease, venous clots | No significant difference | — |
On bone density, the label reports a 2.6% rise in lumbar spine density after 2 years on 2.5 mg, with smaller gains at the hip (Livial SmPC).
Breast cancer survivors: the LIBERATE trial
LIBERATE tested whether tibolone was safe for women with hot flushes after breast cancer surgery. It randomized 3,148 women to tibolone 2.5 mg or placebo; 3,098 were analyzed (Kenemans et al., Lancet Oncol 2009).
| Outcome (median 3.1 years) | Tibolone | Placebo |
|---|---|---|
| Breast cancer recurrence | 237 of 1,556 (15.2%) | 165 of 1,542 (10.7%) |
| Hazard ratio | 1.40 (95% CI 1.14–1.70), p = 0.001 | — |
The trial was designed to show tibolone was not worse than placebo; instead it showed a 40% higher recurrence risk. Hot flushes and bone density improved with tibolone. As a result, past or suspected breast cancer is a contraindication on the label (Livial SmPC).
Endometrium
In the THEBES trial, 3,240 women were randomized to tibolone 1.25 mg, tibolone 2.5 mg or conjugated estrogens plus medroxyprogesterone acetate for up to 2 years (Archer et al., JCEM 2007). At the study end point, no hyperplasia or cancer of the uterine lining was found on either tibolone dose, and absence of bleeding was more common with tibolone (78.7% and 71.4%) than with the comparator (44.9%).
Other data point the other way. In LIFT, 4 endometrial cancers occurred on tibolone and none on placebo, which the label translates into 0.8 extra cases per 1,000 women per year of use. The label also notes that observational studies consistently show a higher endometrial cancer risk in routine use, rising with duration (Livial SmPC).
Sexual function
In a 24-week double-blind trial in 403 women with sexual dysfunction, tibolone 2.5 mg and an estradiol/norethisterone acetate patch both improved Female Sexual Function Index scores (Nijland et al., J Sex Med 2008). Tibolone did better in the per-protocol analysis but not in the intention-to-treat analysis, and satisfying sexual events rose similarly in both groups.
Muscle and body composition
There are no trials of tibolone in men or in people trying to build muscle. The trials in postmenopausal women show little effect on muscle:
| Study | Design | Result |
|---|---|---|
| Ribom et al., Menopause 2011 | RCT, 80 women aged 60+, tibolone 1.25 mg vs placebo, 6 months | No difference in handgrip, knee-extensor strength or chair-stand time |
| Jacobsen et al., J Am Med Dir Assoc 2012 | RCT, women over 70, tibolone 1.25 mg vs raloxifene vs placebo | Bone density rose; no effect on handgrip strength. The tibolone arm was stopped early in 2006 after the LIFT stroke findings |
| Boyanov & Shinkov, Maturitas 2005 | Open-label, 44 women, tibolone 2.5 mg vs untreated controls, 1 year | Lean mass +0.8 kg on DXA (not significant); less fat gain than controls |
Is tibolone “an anabolic”? WADA lists it among anabolic androgenic steroids, and one of its metabolites binds the androgen receptor. That is a regulatory and pharmacological classification, not evidence of muscle gain. In the controlled trials above, tibolone did not increase muscle strength in older women, and no trial has studied it for muscle growth.
Side effects and risks
Stroke
Tibolone increases the risk of ischemic stroke from the first year of use. In LIFT, 28 of 2,249 women on 1.25 mg had a stroke versus 13 of 2,257 on placebo (Livial SmPC). Because baseline stroke risk rises with age, the label estimates about 4 extra strokes per 1,000 women aged 50–59 and 13 per 1,000 aged 60–69 over 5 years of use. The Cochrane review rated the pooled stroke evidence very low quality (OR 1.74, 95% CI 0.99–3.04), with most data from LIFT (Formoso et al., Cochrane 2016).
Breast cancer
- After breast cancer: recurrence rose by 40% in LIBERATE (HR 1.40), and the Cochrane review, pooling LIBERATE with a second trial, found OR 1.5 (95% CI 1.21–1.85) (Formoso et al., Cochrane 2016).
- Without prior breast cancer: randomized trials showed no increase (OR 0.52, 95% CI 0.21–1.25; very low-quality evidence), and LIFT showed fewer cases. However, the label cites observational studies, including the Million Women Study, that found higher breast cancer risk with 2.5 mg, rising with duration of use (Livial SmPC).
Lipids
Tibolone lowers HDL (“good”) cholesterol in a dose-dependent way: by 16.7% on 1.25 mg and 21.8% on 2.5 mg after 2 years. Triglycerides and lipoprotein(a) fall, and LDL does not change (Livial SmPC). A 2024 meta-analysis of randomized trials found falls in apolipoprotein A-I (−34.96 mg/dL, 95% CI −42.44 to −27.48) and lipoprotein(a) (−7.49 mg/dL, 95% CI −12.17 to −2.81), with no change in apolipoprotein B (Li et al., Eur J Obstet Gynecol Reprod Biol 2024). The label states the clinical meaning of these changes is not known.
Common side effects
The label lists effects seen significantly more often than with placebo in 21 trials (4,079 women on tibolone, 3,476 on placebo) (Livial SmPC). They include:
- vaginal bleeding or spotting, vaginal discharge and thickening of the uterine lining;
- breast tenderness, lower abdominal or pelvic pain;
- abnormal hair growth and acne;
- weight gain and edema (fluid retention).
Breakthrough bleeding or spotting occurred in 32.6% of women in the first 3 months and 11.6% at 11–12 months. Bleeding that persists beyond 6 months, starts later or continues after stopping should be investigated.
Who should not use it
The label contraindicates tibolone in pregnancy and breastfeeding; known, past or suspected breast cancer; estrogen-dependent cancers; undiagnosed genital bleeding; untreated endometrial hyperplasia; past or current venous clots or known clotting disorders; any history of arterial disease such as heart attack, angina, stroke or TIA; active liver disease; and porphyria (Livial SmPC).
Interactions
- Warfarin and other anticoagulants: tibolone can increase fibrinolytic activity and enhance warfarin’s effect.
- CYP3A4: tibolone moderately changed the kinetics of midazolam, a CYP3A4 substrate. Enzyme inducers such as carbamazepine, rifampicin, barbiturates, hydantoins and St John’s wort may speed its breakdown.
Legal status and use outside medicine
- UK and other countries: a prescription medicine (Livial), first authorised in the UK in March 1991 (Livial SmPC).
- United States: not available (Morga et al., Menopause 2024). Tibolone is not among the anabolic steroids named in the DEA’s Schedule III list (21 CFR 1308.13).
- Sport: tibolone is named in WADA class S1.1 (anabolic androgenic steroids) and is prohibited in and out of competition (WADA 2026 Prohibited List).
Key takeaways
- A menopause drug, not a bodybuilding steroid. Tibolone is approved outside the US for menopausal symptoms and, in some countries, osteoporosis prevention, at 2.5 mg daily.
- One prodrug, three hormone actions. Its metabolites act on estrogen, progesterone and androgen receptors, and it halves SHBG, which raises free testosterone.
- Fewer fractures, more strokes. In LIFT, vertebral fracture risk fell (relative hazard 0.55) but stroke risk roughly doubled (relative hazard 2.19) in women aged 60–85, and the trial was stopped early.
- Unsafe after breast cancer. LIBERATE found a 40% higher recurrence risk, and breast cancer is now a contraindication.
- No evidence of muscle gain. Trials in older women found no effect on muscle strength, and no trial has tested it for muscle growth.
- Banned in sport. WADA lists tibolone as an anabolic androgenic steroid, prohibited at all times.
Sources
- Organon Pharma (UK) Limited. Livial 2.5 mg tablets: Summary of Product Characteristics. Revised February 11, 2025. emc.
- National Center for Biotechnology Information. PubChem Compound Summary for CID 444008, Tibolone. PubChem.
- Kloosterboer HJ. Tibolone: a steroid with a tissue-specific mode of action. J Steroid Biochem Mol Biol. 2001;76(1-5):231–238. PubMed.
- Hofling M, Carlström K, Svane G, et al. Different effects of tibolone and continuous combined estrogen plus progestogen hormone therapy on sex hormone binding globulin and free testosterone levels–an association with mammographic density. Gynecol Endocrinol. 2005;20(2):110–115. PubMed.
- Timmer CJ, Verheul HA, Doorstam DP. Pharmacokinetics of tibolone in early and late postmenopausal women. Br J Clin Pharmacol. 2002;54(2):101–106. PubMed.
- Cummings SR, Ettinger B, Delmas PD, et al. The effects of tibolone in older postmenopausal women. N Engl J Med. 2008;359(7):697–708. PubMed.
- Morga A, Ajmera M, Gao E, et al. Systematic review and network meta-analysis comparing the efficacy of fezolinetant with hormone and nonhormone therapies for treatment of vasomotor symptoms due to menopause. Menopause. 2024;31(1):68–76. PubMed.
- Formoso G, Perrone E, Maltoni S, et al. Short-term and long-term effects of tibolone in postmenopausal women. Cochrane Database Syst Rev. 2016;10(10):CD008536. PubMed.
- Kenemans P, Bundred NJ, Foidart JM, et al. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Lancet Oncol. 2009;10(2):135–146. PubMed.
- Archer DF, Hendrix S, Gallagher JC, et al. Endometrial effects of tibolone. J Clin Endocrinol Metab. 2007;92(3):911–918. PubMed.
- Nijland EA, Weijmar Schultz WC, Nathorst-Boös J, et al. Tibolone and transdermal E2/NETA for the treatment of female sexual dysfunction in naturally menopausal women: results of a randomized active-controlled trial. J Sex Med. 2008;5(3):646–656. PubMed.
- Ribom EL, Svensson P, van Os S, et al. Low-dose tibolone (1.25 mg/d) does not affect muscle strength in older women. Menopause. 2011;18(2):194–197. PubMed.
- Jacobsen DE, Melis RJ, Verhaar HJ, et al. Raloxifene and tibolone in elderly women: a randomized, double-blind, double-dummy, placebo-controlled trial. J Am Med Dir Assoc. 2012;13(2):189.e1–7. PubMed.
- Boyanov MA, Shinkov AD. Effects of tibolone on body composition in postmenopausal women: a 1-year follow up study. Maturitas. 2005;51(4):363–369. PubMed.
- Li C, Wei M, Mo L, et al. The effect of tibolone treatment on apolipoproteins and lipoprotein (a) concentrations in postmenopausal women: a meta-analysis of randomized controlled trials. Eur J Obstet Gynecol Reprod Biol. 2024;292:8–16. PubMed.
- World Anti-Doping Agency. 2026 Prohibited List, class S1.1 Anabolic Androgenic Steroids. In effect January 1, 2026. WADA 2026 Prohibited List.
- Drug Enforcement Administration. Schedule III. 21 CFR 1308.13. 21 CFR 1308.13.