HRT is contraindicated in about 10% of women with menopausal symptoms (those with a history of or high risk for breast cancer, coronary heart disease, stroke or venous thrombosis) and many others prefer different approaches, so it is important to consider the alternatives.
Tibolone is a synthetic steroid with tissue-specific effects. Its metabolites have different binding affinities for estrogen, progesterone and androgen receptors. It is as effective as HRT for relieving menopausal symptoms without stimulating the endometrium. After tibolone use improvement in mood and libido were reported and there is added benefit of bone protection. There seem to be no increase in venous thrombosis with tibolone. The mammographic density does not increase with tibolone, unlike with HRT. Tissue studies have confirmed markedly reduced growth of breast cells and even of breast cancer cell lines after tibolone. All the above theoretical breast protective effects placed tibolone as good alternative to conventional HRT. Therefore data from the Million Women Study which documented the same increase in risk of breast cancer with tibolone as with estrogen alone came as a surprise. However no analysis was done in relation to possible previous exposure to estrogen and progestogen in these women. One should also take into consideration the fact that tibolone has for many years been preferably prescribed to high risk patients, such as women with benign breast disease, those who had breast tenderness on conventional HRT preparations or those with family history of breast cancer.
Clonidine, a centrally acting a-adrenergic agonist. In doses of 50 to 400 mcg per day it decreases the frequency, severity and duration of hot flushes, without any significant change in blood pressure or pulse rate. The mean rate of flushing was decreased by 46% but this was mainly in cases using 400 mcg. However, with this dosage there were also side effects such as insomnia, syncope and dry mouth.
Lofexidine, another a-adrenergic agonist decreases hot flushes by around 60% in a doses of 0.1 mg up to a maximum dose of 1.6 mg twice daily. Side effects of this drug are dry mouth, fatigue, headache.
Newer antidepressants, such as selective serotonin-reuptake inhibitors and inhibitors of norepinephrine reuptake, are promising non-hormonal treatments for hot flushes. Randomized placebo-controlled trials have shown that venlafaxine, fluoxetine and paroxetine are effective in control of hot flushes.
Gabapentin in the dose of 900mg daily has been shown to reduce significantly hot flushes.