Progestogen use in women approaching the menopause and breast cancer risk

OBJECTIVE: Progestogens, particularly synthetic progestins, are widely used to contrast the clinical consequences of the relative hyperestrogenism that characterizes the years preceding the menopause. As a large body of data on postmenopausal hormone therapy (HT) demonstrates that the addition of synthetic progestins to estrogen increases the breast cancer risk compared to estrogen alone, it is important to evaluate if the use of progestogens in premenopausal years is associated with the risk of breast cancer. METHODS: Main literature data on the association with breast cancer risk of progestogens, either used alone in premenopausal years or added to estrogen in postmenopausal HT, were reviewed. RESULTS: Available data suggest that long-term current use of progestogens in premenopausal women after the age of 40 years can increase the risk of breast cancer. Consistently with the data on postmenopausal HT, the risk increase is higher for lobular cancer than for ductal cancer. CONCLUSIONS: The most important and widely accepted indications to the use of progestogens in the years preceding the menopause are anovulatory menstrual disorders, for which a limited period of treatment is generally sufficient. Awaiting for further data, when using progestogens for longer periods to treat other problems (endometriosis, cyclical mastalgia, etc.), the possibility of increased breast cancer risk and clinical benefits have to be weighed. Anyway, as micronized progesterone and dydrogesterone, at least when they were used in postmenopausal HT, seem to have, according to a large observational study, a safer risk profile on the breast, the preferential use of these preparations could be suggested.