Tibolone, is used in menopausal hormone therapy and in the treatment of postmenopausal osteoporosis and endometriosis.
Brand name Livial among others.
It is taken by mouth.
Pregnancy category AU: D
Progestogen; Progestin; Estrogen; Androgen; Anabolic steroid
Bioavailability 92%
Protein binding 96.3% to albumin; low affinity for SHBG
Metabolism by
Liver, intestines (hydroxylation, isomerization, conjugation).
Elimination half-life 45 hours.
Excretion Urine: 40%
Feces: 60%
It is used in the treatment of menopausal symptoms like hot flashes and vaginal atrophy, postmenopausal osteoporosis, and endometriosis.
It has positive effects on mood and sexual function and libido in menopause.
Tibolone has greater benefits on libido than standard menopausal hormone therapy, which may be related to its androgenic effects.
Tibolone is associated with low rates of vaginal bleeding and breast pain.
Associated with a significantly decreased risk of breast cancer:
decreased risk was greater than that observed with most of the aromatase inhibitors and selective estrogen receptor modulators that were included in the analysis.
Paradoxically, other research has found evidence supporting an increased risk of breast cancer with tibolone.
Available in the form of 2.5 mg oral tablets.
It is typically used once daily at a dosage of 1.25 or 2.5 mg.
Tamoxifen, raloxifene, and tibolone used to reduce the risk of breast cancer, significantly reduces the occurrence of invasive breast cancer in midlife and older women, but also increase the risk of adverse effects.
Tibolone can infrequently produce androgenic side effects such as acne and increased facial hair growth: 3 to 6% of treated women.
Possible adverse effects of tibolone include unscheduled vaginal bleeding (13–26%) more than placebo, an increased risk of breast cancer in women with a history of breast cancer, although apparently not without a history of breast cancer, an increased risk of strokes and cardiovascular events, and an increased risk of endometrial cancer.
Tibolone has been associated with increased risk of endometrial cancer in most studies.
Δ4-Tibolone, one of the active metabolites of tibolone.
It has weak estrogenic, progestogenic, and androgenic activity.
Tibolone, acts as agonists of the estrogen receptors.
Tibolone and its metabolite δ4-tibolone act as agonists of the progesterone and androgen receptors.
Other metabolites act as antagonists of these receptors.
Tibolone, including its metabolites, has been described as possessing moderate functional antiestrogenic activity that is, progestogenic activity, moderate estrogenic activity, high androgenic activity, and no clinically significant glucocorticoid, antiglucocorticoid, mineralocorticoid, or antimineralocorticoid activity.
Its ovulation-inhibiting dosage of tibolone is 2.5 mg/day.
Tibolone and its two major metabolites, are potent, fully activating agonists of the estrogen receptor (ER), with a high preference for the ERα.
The estrogenic effects have desirable effects in bone, the brain, and the vagina, and lack of undesirable action in the uterus, breast, and liver.
Tibolone has also been described as a selective progestogen, estrogen, and androgen regulator: SPEAR.
It regulates effects not only of estrogens but of all three of the major sex hormone classes.
Paradoxically, associated with increased risk of endometrial cancer and breast cancer in clinical studies.
Aromatase inhibitor had no effect on the estrogenic potencies of tibolone or its metabolites.
Tibolone decreases sex hormone-binding globulin (SHBG) levels by 50% in women and does not increase the risk of venous thromboembolism.
Tibolone acts as agonist of the progesterone receptor.
Its weak progestogenic activity may not be sufficient to fully counteract estrogenic activity of tibolone in the uterus and may be responsible for the increased risk of endometrial cancer that has been observed with tibolone in women in large cohort studies.
Tibolone has androgenic activity.
Relative to other 19-nortestosterone progestins, the androgenic activity of tibolone is high, with a potency comparable to that of testosterone.
The androgenic effects of tibolone may reduce breast cell proliferation, reduced breast cancer risk, improve sexual function, lesser unfavorable changes in hemostatic parameters relative to estrogen–progestogen combinations, and changes in liver protein synthesis, 30% reductions in HDL cholesterol levels, 20% reduction in triglyceride levels, and 50% reduction in SHBG levels.
Its androgenic side effects include acne and increased hair growth in some women.
Tibolone, and it’s metabolites act as antagonists of the glucocorticoid and mineralocorticoid receptors, with preference for the mineralocorticoid receptor.
The mean oral bioavailability is 92%.
Its plasma protein binding is 96.3%.
Tibolone and its metabolites have low affinity for SHBG.
It is metabolized in the liver and intestines.
It is a prodrug and is rapidly transformed into several metabolites.
Its half-life is 45 hours.
It is excreted in urine 40% and feces 60%.
It is not available in the United States.