Regimens for hormone replacement therapy

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Dr D. Palmer, the author of the article, comments:

Oestrogen is recommended as unopposed therapy for women post-hysterectomy because it is the specific medication required to relieve symptoms and to protect against future disease. Progestogens were added to HRT regimens after being shown to protect against the increased risk of endometrial carcinoma. While it may be logical to include progestogens in all HRT regimens to mimic the premenopausal hormone profile, their effect on breast tissue remains unclear and they have associated problems.

There is debate whether progestogens antagonise the effect of oestrogen on breast tissue in the way that they protect endometrium. It is uncertain whether the increased mitotic activity in breast epithelium in the luteal phase of the cycle is a concern when using exogenous progestogen.²

A recent meta-analysis of 4 studies³ specifically addressed the hypothesis that the addition of progestogen to oestrogen reduces the risk of breast cancer. Contrary to Gambrell's earlier study⁴ (which did not adjust for age), use of combined HRT did not reduce the overall slight increase in relative risk of breast cancer.

Progestogenic adverse effects, while not life-threatening have been suggested as being one of the most important reasons for women stopping HRT.⁵ The potential adverse effects of progestogens on lipid profiles and attenuation of the beneficial effect of oestrogen on cardiovascular disease are controversial. These have not been significant in most short-term studies, but long-term results are not available.

Thus, despite limited data suggesting addition of progestogen may protect against breast cancer, most authorities⁶ would consider the data insufficient to warrant progestogen use in women who have had a hysterectomy; especially in view of the small but real incidence of adverse effects and the theoretical adverse effects on lipid profile.