What are the problems with tibolone?

October 8, 2025 •

4 min read

Studies have shown that for women over 60, tibolone use is associated with a significantly increased risk of stroke. This is one of the most serious problems with tibolone, a synthetic steroid used to treat menopausal symptoms and osteoporosis. While it offers benefits, the potential for severe health complications requires careful consideration of the risks versus rewards.

Quick Summary

Tibolone, while effective for menopause symptom relief, has notable risks, including increased stroke risk in older women and higher breast cancer recurrence in those with a history of the disease.

Key Points

Increased Stroke Risk: Tibolone significantly raises the risk of stroke, especially in women over 60, with the risk increasing early in treatment.
Breast Cancer Recurrence: The medication is contraindicated in women with a history of breast cancer, as it increases the risk of recurrence.
Higher Endometrial Cancer Risk: There is an increased risk of developing endometrial cancer, particularly with prolonged tibolone use in women with an intact uterus.
Common Side Effects: Users frequently report side effects like breast tenderness, headaches, stomach pain, and vaginal bleeding, especially during the initial months.
Drug Interactions and Contraindications: Tibolone interacts with drugs like warfarin and liver enzyme inducers, and should not be used in women with a history of blood clots, certain cancers, or active liver disease.
Androgenic Effects: Due to its androgenic metabolites, tibolone can cause androgen-related side effects such as unusual hair growth or acne.

Tibolone is a synthetic steroid widely used in many countries as a hormone replacement therapy (HRT) alternative for postmenopausal women. It works through metabolites that have estrogenic, progestogenic, and androgenic effects, providing relief from symptoms like hot flashes and vaginal dryness, and helping to prevent osteoporosis. However, as with any potent medication, it is not without significant problems and risks that must be carefully evaluated by both patients and healthcare providers.

Significant Cardiovascular and Thromboembolic Risks

One of the most critical issues with tibolone is its association with an increased risk of stroke, particularly in women aged 60 and over. The Long-Term Intervention on Fractures with Tibolone (LIFT) trial, which studied older women with osteoporosis, found a more than twofold increased risk of stroke in the tibolone group compared to placebo. This heightened risk is a major reason why the drug's use is often discouraged in elderly populations.

Stroke: The increased risk, which appears to be greater in the first year of treatment, led to the premature stopping of the LIFT trial.
Venous Thromboembolism (VTE): While some studies suggest no increased risk compared to combined HRT, the potential for blood clots is a known concern for all hormonal therapies, and caution is warranted, especially in women with a history of thromboembolic disorders.
Coronary Heart Disease: While data is less conclusive, the increased stroke risk raises biological plausibility for an elevated risk of coronary events.

Increased Risk of Certain Cancers

Despite early beliefs that tibolone might be safer for the breast than some forms of HRT, subsequent studies have uncovered significant risks related to certain cancers.

Breast cancer

The relationship between tibolone and breast cancer risk is complex and has been a subject of evolving research.

Recurrence Risk: In the LIBERATE study, tibolone increased the risk of breast cancer recurrence in women with a prior history of the disease, causing the trial to be stopped. For this reason, tibolone is contraindicated in women with current or suspected breast cancer.
Risk in Healthy Women: Observational data, such as the Million Women Study, found a moderately increased risk of breast cancer diagnosis in healthy tibolone users, comparable to oestrogen-only HRT but lower than combined HRT. However, recent studies on Asian populations suggest no increased risk, highlighting potential ethnic variations or limitations in earlier research.

Endometrial cancer

Increased Incidence: Studies have shown an increased risk of endometrial cancer, particularly with prolonged use of tibolone in women with an intact uterus.
Vaginal Bleeding: Unscheduled vaginal bleeding or spotting, especially if it continues beyond the initial months of treatment, requires gynecological investigation to rule out endometrial malignancy.

Common and Minor Side Effects

In addition to the serious risks, tibolone is associated with a range of less severe but still problematic side effects. These often improve within the first few months of treatment, but can affect a patient's quality of life.

Common Side Effects: Breast tenderness, abdominal or pelvic pain, and headaches are frequently reported.
Androgenic Effects: Due to its androgenic metabolites, tibolone can cause unwanted hair growth (hirsutism) or acne.
Vaginal Issues: Patients may experience vaginal itching, discharge, or spotting, especially in the early stages of treatment.
Cholesterol Changes: Tibolone is known to decrease levels of high-density lipoprotein (HDL) cholesterol, though the clinical implications of this are not fully understood.

Important Contraindications and Drug Interactions

To mitigate risks, tibolone is not suitable for all women. There are clear medical conditions that contraindicate its use.

Contraindications: The medication should not be used in women with a history of or active venous or arterial thromboembolic disease, known or suspected estrogen-dependent cancers (like breast or endometrial), undiagnosed vaginal bleeding, acute liver disease, or porphyria.
Drug Interactions: Tibolone can interact with other medicines. For example, it may enhance the effects of anticoagulants like warfarin, increasing the risk of bleeding. Liver enzyme inducers, such as phenytoin, carbamazepine, rifampicin, and St. John's Wort, can reduce the effectiveness of tibolone.

Tibolone vs. Conventional HRT

Understanding the problems with tibolone requires comparing its risk profile with conventional HRT, which includes estrogen-only and combined estrogen-progestogen therapies.


Feature	Tibolone	Conventional Combined HRT
Mode of Action	Synthetic steroid with estrogenic, progestogenic, and androgenic effects.	Contains separate estrogen and progestogen components.
Effect on Endometrium	Minimal stimulation; generally low rates of vaginal bleeding.	Requires progestogen to counteract estrogenic stimulation, which can cause unscheduled bleeding.
Effect on Breast Tissue	Possibly lower risk of breast cancer than combined HRT in healthy women, but clearly increases recurrence risk in those with a history of breast cancer.	Can increase breast cancer risk, especially with long-term use.
Stroke Risk	Significantly increased risk, especially in women over 60.	Modestly increased risk, but still a concern.
Effect on Libido	Often associated with an increase in libido due to its androgenic effects.	Effects can be more variable.
Side Effects	Breast tenderness, stomach pain, vaginal discharge, potential hair growth.	Breast pain, nausea, mood changes, headaches.

Conclusion

While tibolone provides an effective treatment for menopausal symptoms and osteoporosis, its use is not without significant problems. The major concerns revolve around the increased risk of stroke, particularly in women over 60, and the heightened risk of breast cancer recurrence in those with a previous diagnosis. Other issues, such as an increased risk of endometrial cancer with long-term use and common side effects like breast tenderness and vaginal bleeding, also factor into its risk profile. The presence of contraindications, such as active or a history of thromboembolic disease, further limits its applicability. For these reasons, the decision to use tibolone must involve a thorough evaluation of the individual's overall health, risk factors, and treatment priorities, and is often balanced against other available hormone therapies and alternatives. Regular medical follow-ups are essential for monitoring potential adverse effects. You can find more information on the benefits and risks from government health websites and medical reviews.

Frequently Asked Questions

Tibolone is contraindicated for women with a history of or active breast cancer, endometrial cancer, or other estrogen-dependent malignant tumors. It should also be avoided by those with a history of blood clots, stroke, unexplained vaginal bleeding, or acute liver disease.

Yes, research has shown that tibolone significantly increases the risk of stroke, especially in women aged 60 years or older. This heightened risk was a key finding in the LIFT trial.

Common side effects include breast tenderness, stomach or pelvic pain, headaches, and vaginal bleeding or spotting. Many of these effects tend to lessen over the first few months of treatment.

No, tibolone is not recommended for women with a known, past, or suspected breast cancer. Studies have shown it increases the risk of recurrence, and its use is contraindicated in this group.

While some observational studies suggested a potentially lower risk of breast cancer in healthy women compared to combined HRT, other data indicates an increased risk with tibolone. Importantly, it significantly increases recurrence risk in women with a breast cancer history.

Tibolone has been associated with a mean increase in weight, and some women may gain a significant amount of weight while on the medication. However, conventional HRT alternatives can also affect body weight.

Tibolone can increase the effect of anticoagulants like warfarin, and its effectiveness can be reduced by liver enzyme-inducing drugs such as phenytoin, carbamazepine, and rifampicin. Caution is advised when combining these medications.