Progestogens are the problem in hormone replacement therapy: Time to reappraise their use

Abstract

Combined (estrogen and a progestogen) hormone replacement therapy (cHRT) is associated with an increased risk of breast cancer, while estrogen replacement therapy is not. Whatever the underlying mechanism, it is the progestogen in cHRT that seems to increase the risk. Fear of breast cancer is a major limiting factor in the use of hormone replacement therapy, and when women discontinue cHRT because of side effects, the latter are often attributable to the progestogen component. cHRT is given to women with an intact uterus to protect against the effects of un-opposed estrogen such as an increased risk of endometrial cancer. Estrogen replacement therapy suffices for women with a prior hysterectomy. There is a clear distinction in risk and side effect profile between cHRT and estrogen replacement therapy. Apart from being the most effective treatment for menopausal symptoms, estrogen prevents osteoporosis, and may also have a potential role in prevention of Alzheimer’s Dementia, now the biggest killer of women in the United Kingdom. Evidence also suggests that progestogens could compromise the dementia-preventative effect of estrogen. Given the immense therapeutic and preventative potential of estrogen, the use of progestogens in cHRT needs re-appraisal. The levonorgestrel intrauterine system (LNg-IUS) could reduce breast cancer risk while protecting the endometrium. Other approaches to the safe use of progestogens await research.