Tibolone
[CAS# 5630-53-5]

Identification

• Classification: API >> Hormone and endocrine-regulating drugs >> Birth control pills
• Name: Tibolone
• Synonyms: 17-Hydroxy-7alpha-methyl-19-norpregn-5(10)-en-20-yn-3-one
• Molecular Formula: C₂₁H₂₈O₂
• Molecular Weight: 312.45
• CAS Registry Number: 5630-53-5
• EC Number: 227-069-1
• SMILES: C[C@@H]1CC2=C(CCC(=O)C2)[C@@H]3[C@@H]1[C@@H]4CC[C@]([C@]4(CC3)C)(C#C)O

Properties

• Melting point: 165-169 °C

Safety Data

• Hazard Symbols: HGS07;HGS08 Danger
• Risk Statements: H319--H351-H360fd-H372
• Safety Statements: P203-P260-P264-P264+P265-P270-P280-P305+P351+P338-P318-P319-P337+P317-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Carcinogenicity	Carc.	2	H351
Reproductive toxicity	Repr.	1B	H360Fd
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Reproductive toxicity	Repr.	2	H361
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H332
Reproductive toxicity	Repr.	1B	H360
Acute toxicity	Acute Tox.	4	H312

Discovery and Applications

Tibolone is a tissue-selective anabolic steroid used primarily for hormone replacement therapy (HRT) in postmenopausal women. Tibolone, chemically known as 7α-methyl-17α-ethynyl-19-norethindrone-5(10)-en-3β-ol, was developed in the 1960s as a selective estrogen receptor modulator (SERM) with tissue-specific action. It is designed to provide estrogenic, progestogenic, and androgenic activities while minimizing potential side effects associated with conventional hormone therapy.

Tibolone is a synthetic steroid derived from norethindrone that has been modified to include an ethynyl group at the C17α position. This modification improves its oral bioavailability and prolongs its metabolic stability in vivo. Tibolone, as a prodrug, is metabolized to three active metabolites: Delta4-tibolone, 3α-hydroxytibolone, and 3β-hydroxytibolone. These metabolites exert tissue-selective effects on estrogen receptors (ER), androgen receptors (AR), and progesterone receptors (PR) in different tissues: In bone tissue, tibolone and its metabolites have estrogen-like effects that help prevent bone loss and reduce the risk of osteoporotic fractures in postmenopausal women. In the endometrium, the progestogenic effects of tibolone counteract estrogen-induced proliferation, reducing the risk of endometrial cancer associated with estrogen therapy alone. The androgenic effects of tibolone help improve sexual health, including increased libido and vaginal lubrication, which are common problems in postmenopausal women.

Tibolone is used to relieve symptoms associated with menopause, including hot flashes, night sweats, mood swings, and vaginal dryness. Its ability to relieve these symptoms stems from its combined estrogen, progestin, and androgen effects. Tibolone is particularly beneficial for postmenopausal women at risk for osteoporosis. By maintaining bone density through its estrogen-like effects on bone tissue, tibolone helps reduce the incidence of fractures and preserve bone health.

Unlike traditional estrogen monotherapy, tibolone does not increase the risk of cardiovascular events in postmenopausal women. It has a good cardiovascular safety profile and is therefore the first choice for women who are concerned about heart health. The progestogenic effects of tibolone on the endometrium are associated with a lower risk of endometrial hyperplasia and cancer compared with estrogen monotherapy. However, its use in women with a history of breast cancer still requires caution due to potential hormonal effects.

Common side effects of tibolone include headache, vaginal bleeding, breast tenderness, and gastrointestinal disturbances. Serious side effects are rare but may include thromboembolic events and liver dysfunction, which require careful monitoring during treatment. Tibolone is contraindicated in pregnant women, patients with liver disease, patients with thromboembolic disease, or patients with a history of hormone-dependent cancer. Women with cardiovascular risk factors should use it with caution.

References

2004. Tibolone: a unique molecule for the treatment of menopausal symptoms. Gynecological Endocrinology, 18(4).
DOI: 10.1080/09513590400020963

2002. Tibolone: clinical applications and experience. Endocrinology and Metabolism Clinics of North America, 31(3).
DOI: 10.1016/s0889-8529(02)00056-7

2000. Tibolone and breast cancer risk. European Journal of Cancer, 36(8).
DOI: 10.1016/s0959-8049(00)00236-7