Progestogens are the problem in HRT : Time to reappraise

Posted on 31st December 2019

Progestogens are the problem

in hormone replacement therapy:

Time to reappraise their use

Isaac Manyonda1, Vikram S Talaulikar2 , Roxanna Pirhadi3,

and Joseph Onwude4


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.

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