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What are the Effects of Progesterone on Heart Disease in Hormone Therapy?

Hormone therapy is frequently prescribed to women to lessen the risk of cancer and cardiovascular disease, but what is the evidence of the effects of progesterone?

The risk of cardiovascular disease increases significantly in women after the onset of menopause, which also leads to changes in blood cholesterol levels. Hormone replacement therapy has long been shown to protect against cardiovascular disease, particularly through its estrogen content. Another hormone, progesterone, has been included in hormone replacement therapy to decrease the risk of cancer in the reproductive organs, but recent clinical trials suggest that the combination of estrogen and progesterone may actually increase the risk of both cardiovascular disease and cancer.

Progesterone refers to a natural progestogen frequently used in hormone therapies, but there are many synthetic progesterone-like hormones, or progestins, as well. Humans have two progesterone receptors, and progesterone can alter gene transcription into proteins through other more generalized steroid receptors. The specific configuration of each progesterone or progestin molecule may determine how these receptors are interacting with the hormone.

To address the effects of progesterone on cardiovascular disease, Jiang and Tian undertook a review of published research quantifying the effects of progesterone on a variety of metabolic molecules. The recently published the findings in Lipids in Health and Disease.

The review showed that progesterone molecules that are more like androgens tend to negate the positive effects of estrogen on cardiovascular disease risk. However, several clinical trials have shown that this is not mediated through changes to blood cholesterol or triglyceride levels, although different progestins may have somewhat different effects and interactions with estrogen in this regard. More long-term data from clinical trials are necessary to determine what the effects of different progestins are on blood lipid levels.

Written by C. I. Villamil

Reference: Jiang and Tian 2017 The effects of progesterones on blood lipids… Lipids in Health and Disease 16:219

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