Tibolone is a synthetic steroid drug mainly used to manage menopausal symptoms like hot flashes and to help prevent osteoporosis after menopause. It is a form of hormone replacement therapy that functions by imitating the actions of estrogen, progesterone, and testosterone in the body. Once absorbed, tibolone is broken down into active metabolites that exert varying effects on different tissues, offering mild estrogenic, progestogenic, and androgenic activities.
BRAND NAMES:
Livial: is a well-known brand name for tibolone, as also mentioned by.
Tibofem, manufactured by Cipla Ltd., is another brand name.
Maxtib, from Sun Pharmaceutical Industries Ltd., is also available.
MECHANISM OF ACTION
Tibolone’s effects are primarily due to the activity of its metabolites in various tissues. After oral administration, tibolone is rapidly metabolized into three main compounds: 3α-hydroxy-tibolone and 3β-hydroxy-tibolone, which exhibit estrogen-like activity, and the Δ4-isomer, which has progestogenic and androgenic properties. The tissue-specific effects of tibolone arise from its unique metabolism, local enzyme regulation, and differential receptor activation in various parts of the body. Its bone-protective effects are attributed to the activation of estrogen receptors, with no involvement of progesterone or androgen receptors in this process. Unlike traditional estrogen-progestogen therapies, tibolone does not stimulate breast tissue in primate models. This is believed to be due to tibolone and its metabolites inhibiting the enzymes sulphatase and 17β-hydroxysteroid dehydrogenase (HSD) type I, while promoting the activity of sulphotransferase and 17β-HSD type II. Together, these actions reduce the formation of active estrogens.
PHARMACOKINETICS
Absorption:
Tibolone is a prodrug that is rapidly and extensively absorbed after oral administration. The parent compound is quickly metabolized in the gastrointestinal tract and liver into three active compounds, so its plasma concentrations remain very low.
Distribution:
Tibolone is a synthetic steroid that is rapidly metabolized into three active metabolites: 3α-hydroxytibolone, 3β-hydroxytibolone, and the Δ4cap delta to the fourth powerΔ4-isomer. The distribution of these metabolites is highly tissue-selective, enabling tibolone to have different hormonal effects in various parts of the body.
Metabolism
Tibolone is rapidly converted into three major metabolites: 3 alpha- and 3 beta-hydroxy-tibolone, which have oestrogenic effects, and the Delta (4)-isomer, which has both progestogenic and androgenic effects.
Excretion:
Tibolone and its metabolites are primarily excreted through the urine, with a smaller portion eliminated via the feces. After oral administration, the drug undergoes extensive metabolism, and the resulting inactive and active metabolites are cleared from the body mainly through renal pathways.
PHARMACODYNAMICS
Tibolone helps prevent bone loss and effectively treats postmenopausal symptoms without stimulating the endometrial tissue, which is important since endometrial stimulation can lead to malignancy. In contrast, traditional estrogen therapies used for menopause often promote endometrial cell proliferation, increasing the risk of endometrial cancer. The beneficial effects of tibolone on bone, brain, and vaginal tissues are attributed to its estrogen-like activity. However, this estrogenic effect does not occur in the endometrium. Unlike combined estrogen-progesterone therapies, tibolone also acts differently on breast tissue. Because of these tissue-specific actions, tibolone is considered a selective estrogen activity regulator (SEAR).
ADMINISTRATION
Tibolone is administered orally, typically in the form of 2.5 mg tablets taken once daily. It is intended for continuous use without breaks, and can be taken with or without food. The treatment is usually prescribed to postmenopausal women, typically those who are at least 12 months past their last menstrual period. Before starting therapy, a thorough medical assessment is recommended, including evaluation of personal and family history, especially in relation to hormone-sensitive cancers or cardiovascular conditions. Regular follow-ups are advised to assess the ongoing benefit-risk balance during treatment.
DOSAGE AND STRENGTH
Tibolone is available in specific oral tablet strengths, and the prescribed dosage may vary based on an individual's medical condition and risk factors. It is essential to consult a healthcare professional before starting tibolone. This information is intended for general awareness and should not be considered medical advice.
DRUG INTERACTIONS
Some medications may influence the way tibolone works. Tell your doctor or pharmacist if you're taking any of these medicines before you start taking tibolone: medicines that help to prevent blood clots, such as warfarin. Medications used to treat epilepsy, such as phenytoin or carbamazepine.
FOOD INTERACTIONS
Tibolone generally has no significant food interactions, meaning it can be taken with or without food. However, it’s always best to follow your healthcare provider’s instructions regarding how to take the medication. If you notice any unusual effects when taking tibolone with certain foods, be sure to inform your doctor.
CONTRAINDICATIONS
Here are some common contraindicationsfor tibolone:
Known or suspected breast cancer.
Undiagnosed vaginal bleeding.
Active or history of blood clots (such as deep vein thrombosis or pulmonary embolism).
Liver disease or impaired liver function.
Known or suspected hormone-sensitive cancers (like certain types of ovarian or endometrial cancer).
Pregnancy or breastfeeding.
Hypersensitivity to tibolone or any of its ingredients.
It’s important to discuss your full medical history with your healthcare provider before starting tibolone to ensure it is safe for you.
SIDE EFFECTS
Breast tenderness or pain
Vaginal bleeding or spotting
Abdominal pain or cramps
Headache
Weight gain
Mood changes or depression
Acne or oily skin
OVER DOSE
An overdose of Tibolone can cause symptoms like nausea, dizziness, and vaginal bleeding. If any of these symptoms occur, it is essential to seek medical attention immediately.
If you forget to take a dose of Tibolone, take it as soon as you remember. However, if it is nearly time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not take two tablets to compensate for a missed dose.
TOXICITY
In long-term oral carcinogenicity studies involving rodents, tibolone treatment was associated with an increased incidence of various tumors. These included pituitary adenomas, mammary carcinomas and fibroadenomas, hepatic adenomas, uterine carcinoma, stromal polyps and stromal sarcomas, as well as carcinomas of the urinary bladder and testes. However, tibolone did not demonstrate any genotoxic effects in studies assessing gene mutations, chromosomal damage, or DNA damage.
