Tibolone
A synthetic steroid whose metabolites have estrogenic, progestogenic and androgenic activity, giving tissue-selective effects. Used as single-agent menopausal HRT for vasomotor symptoms, bone protection and libido without needing a separate progestogen.
01 Overview
Tibolone is a synthetic 19-nortestosterone-derived steroid that acts as a prodrug: it is metabolised into three compounds with estrogenic, progestogenic and androgenic activity respectively. This gives tissue-selective action, relieving menopausal symptoms and preserving bone while the progestogenic metabolite protects the endometrium, so no separate progestogen is needed. Its androgenic component may improve libido.
Large trials showed benefits for hot flushes and bone density but also raised concerns: increased stroke risk in older women (OPAL/LIFT) and increased breast cancer recurrence in survivors (LIBERATE). It is not approved in the US but used in Europe and elsewhere.
02 Mechanism
Prodrug metabolised to 3-alpha/3-beta-hydroxy (estrogenic) and delta-4 (progestogenic/androgenic) metabolites producing tissue-selective estrogenic, progestogenic and androgenic effects.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Menopausal HRT | 1.25–2.5 mg/day | Oral | 2.5 mg/day standard; 1.25 mg for lower-dose regimens. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Relief of vasomotor symptomsReduces hot flushes and night sweats. | Clinical | ||
| Improved libidoAndrogenic metabolite can enhance sexual desire and mood. | Clinical | ||
| Bone density preservationReduces postmenopausal bone loss and vertebral fracture risk. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Increased stroke riskLIFT trial found increased stroke risk in women over 60. | Life-threatening | Uncommon (older women) | Clinical | |
| Breast cancer recurrenceLIBERATE trial showed increased recurrence in breast cancer survivors. | Severe | Uncommon | Clinical |