Tibolone
Tibolone is a synthetic steroid for postmenopausal HRT with tissue-selective estrogenic, progestogenic and weak androgenic activity. It is widely available in Europe (Livial) but not approved in the United States; one tablet daily covers combined HRT in a single molecule.
- Chemical formula
- C21H28O2
- CAS number
- 5630-53-5
- ATC code
- G03CX01
- Molecular weight
- 312.45 g/mol
- Drug class
- Synthetic steroid (STEAR)
- Also known as
- Livial, Liviel, Tibofem
What is it?
Tibolone is a synthetic steroid drug (STEAR — Selective Tissue Estrogenic Activity Regulator) introduced by Organon in 1988 and marketed primarily as Livial. It is widely used in European, Latin American and Asian markets for postmenopausal hormone replacement therapy, but has never been approved by the FDA. Authorised generic tibolone is available in many markets. Its appeal is that one daily tablet covers the role of combined estrogen + progestin HRT, with its three active metabolites providing balanced tissue-selective activity.
Mechanism of action
Tibolone is a prodrug; on absorption it is rapidly converted to three active metabolites (3α-OH-tibolone, 3β-OH-tibolone and Δ4-tibolone) with different tissue-selective activity. The hydroxylated metabolites have estrogenic activity in bone, vagina and brain (relieving menopausal symptoms and protecting bone), while the Δ4 metabolite has progestogenic and weak androgenic activity (protecting the endometrium and supporting libido). This selectivity is the basis for tibolone's positioning as a balanced HRT alternative.
Pharmacokinetics
Tibolone is rapidly absorbed and almost completely converted to its active metabolites with low parent drug exposure. The hydroxylated metabolites have half-lives of ~6 hours; the Δ4 metabolite is shorter. Once-daily dosing is sufficient. Hepatic conjugation predominates. Strong enzyme inducers may reduce tibolone effect; the metabolite system is moderately complex.
Indications
Tibolone is approved (in countries where licensed) for treatment of moderate-to-severe vasomotor menopausal symptoms and prevention of postmenopausal osteoporosis in women at least 12 months past their last natural menstrual period. According to current menopause guidelines in markets where tibolone is available, it is considered a reasonable alternative to combined estrogen-progestin HRT, particularly in women who prefer simpler dosing or want some libido benefit from the weak androgenic activity.
Safety profile
Common adverse effects include vaginal bleeding or spotting (especially in the first 3 months), breast tenderness, weight changes, headache and dizziness. The LIFT trial (2008) found that tibolone reduced fracture and breast cancer risk in older women but increased stroke risk in women over 60, leading to age-restricted use in many markets. Tibolone should not be started after age 60 or more than 10 years past menopause. Endometrial bleeding warrants prompt evaluation.
Products containing this ingredient
Frequently asked questions
How is tibolone different from standard HRT? ▾
Standard HRT uses estradiol or conjugated estrogens combined with a progestogen, in two separate active ingredients. Tibolone is a single synthetic steroid that converts to estrogenic, progestogenic and weak androgenic metabolites in a tissue-selective manner. The practical difference is one tablet daily versus two components, plus modest libido benefit from androgenic activity. According to current menopause guidelines, both approaches are reasonable in markets where tibolone is available.
Why is tibolone not approved in the United States? ▾
Tibolone has been used in Europe since 1988 but the manufacturer never sought FDA approval, partly because the regulatory development pathway for combination effects is complex and the US market favoured separate estrogen + progestogen products. According to current US menopause guidelines, US prescribers do not have access to tibolone and use combined estradiol + micronised progesterone instead.
Is tibolone safer than combined HRT? ▾
Tibolone has a similar overall safety profile to combined HRT — small increases in stroke (especially over 60), VTE and a complex breast cancer signal that may be slightly more favourable than estrogen + medroxyprogesterone HRT. The LIFT trial showed reduced breast cancer recurrence in early-stage cancer survivors but increased stroke risk. According to current European menopause guidelines, tibolone is restricted to women under 60 within 10 years of menopause.
The information on this website is provided for reference and educational purposes only. It does not replace consultation with a qualified healthcare professional.