Tibolone Dosage and Contraindications for Hormone Replacement Therapy
The recommended dosage of tibolone for hormone replacement therapy is 2.5 mg daily, with 1.25 mg daily as an alternative lower dose option that may have similar efficacy with potentially better tolerability. 1, 2
Dosage Information
- The standard therapeutic dose of tibolone is 2.5 mg daily, which effectively reduces menopausal symptoms including hot flashes, sweating episodes, and vaginal dryness 1, 2
- A lower dose of 1.25 mg daily may provide similar efficacy with potentially fewer side effects, though benefits may occur more gradually than with the 2.5 mg dose 2
- Long-term studies have shown that tibolone 2.5 mg daily maintains its beneficial effects on bone loss over periods as long as 10 years 3
- Tibolone should be administered continuously without interruptions when used for hormone replacement therapy 1
Mechanism and Effects
- Tibolone is a synthetic compound with weak estrogenic, progestogenic, and androgenic actions 1
- It effectively reduces hot flashes and improves vaginal dryness in postmenopausal women 1
- Tibolone may improve sexual function more effectively than standard hormone therapy 1
- In the breast, tibolone inhibits the enzyme sulfatase, which regulates estrogen formation and decreases estrogen stimulation 1
- Studies show tibolone causes less breast tenderness and mammographic density changes compared to conventional hormone replacement therapy 1, 4
- Tibolone increases fibrinolysis parameters without significantly altering coagulation parameters, potentially reducing the risk of venous thrombosis compared to some other HRT options 5
Contraindications
- Breast cancer history is a major contraindication for tibolone use 1, 6
- A large prospective, randomized, placebo-controlled trial (LIBERATE) was halted due to safety concerns when tibolone was used in breast cancer survivors 1
- Tibolone should not be used in patients with:
- Known or suspected estrogen-dependent malignant tumors 6
- Undiagnosed vaginal bleeding 6
- Untreated endometrial hyperplasia 6
- Previous or current venous thromboembolic disorders (deep vein thrombosis, pulmonary embolism) 6
- Known thrombophilic disorders 6
- Active or recent arterial thromboembolic disease (e.g., angina, myocardial infarction) 6
- Acute liver disease or history of liver disease where liver function tests have not returned to normal 6
- Porphyria 6
Advantages Over Other HRT Options
- Tibolone causes significantly less vaginal bleeding in the first 3 months of treatment compared to continuous combined estradiol plus norethisterone acetate (18.3% versus 33.1%) 7
- Lower incidence of breast pain/tenderness compared to conventional HRT (3.2% versus 9.8%) 7
- Does not increase mammographic density, unlike combined HRT, which may compromise the ability of mammography to detect early cancers 1, 4
Monitoring and Follow-up
- Endometrial thickness and breast density should be monitored during treatment 2
- Laboratory tests including lipid profile and blood glucose should be checked periodically 2
- Patients should be evaluated for the occurrence of menopausal symptoms and quality of sexual life to assess treatment efficacy 2
- HRT should generally be continued until the average age of spontaneous menopause (45-55 years) 1
- After menopause age, decisions about continuation should be based on individual risks, family history, and symptom severity 6
Common Side Effects
- Vaginal bleeding (reported in 12-14% of patients) 2
- Breast tenderness (though less frequent than with conventional HRT) 7
- Weight gain, acne, and hirsutism (due to androgenic effects) 1
- Mood changes 8
Tibolone represents a unique option for HRT with specific advantages in terms of bleeding profile and breast effects, but careful consideration of contraindications is essential, particularly regarding breast cancer risk.