September 30, 2019
2 min read

Metabolic effects of HT may limit postmenopausal diabetes risk

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Hormone therapy may slow the development of diabetes among postmenopausal women due to its effects on certain metabolites, according to findings presented at the North American Menopause Society annual meeting.

Heather Hirsch

“There is something metabolically going on when we lose our estrogen. While the story is still ongoing and there’s still a lot more we need to learn, this helped us to say that, ‘Yes, we are going in the right direction. We are seeing some metabolic changes,’” Heather Hirsch, MD, medical director of the specialty menopause clinic and associate physician at Brigham and Woman’s Hospital in Boston, told Endocrine Today. “There probably is a direct reason why metabolism shifts at menopause and why women are more prone to develop chronic diseases at menopause.”

Hirsch and colleagues examined changes in the levels of leucine, isoleucine, valine, phenylalanine, tyrosine, glycine, glutamine, C3-carnitine and C5-carnitine among 1,072 women who took part in the Women’s Health Initiative. As part of the original study, women were randomly assigned to HT with either estrogen, estrogen plus progesterone or placebo. Researchers collected blood samples at baseline and at 1 year. Hirsch and colleagues identified 360 metabolites using these samples but focused on the nine listed above.

“The reason I was really interested in looking at these metabolomics is to start to really look beyond the curtain to see what are the real changes that are happening on the molecular level that show that there’s no coincidence that at about the same time women lose their estrogen, they start to develop some of these chronic diseases,” Hirsch said.

Woman with her Doctor 
Hormone therapy may slow the development of diabetes among postmenopausal women due to its effects on certain metabolites.
Source: Adobe Stock

Among those who received estrogen plus progesterone, Hirsch and colleagues observed a reduction in C3-carnitine, C5-carnitine, glycine, phenylalanine, tyrosine, leucine and valine after 1 year of therapy compared with placebo. Meanwhile, levels of C3-carnitine, C5-carnitine, glycine, phenylalanine and tyrosine all dropped in women who were treated with only estrogen therapy after 1 year compared with placebo. The researchers noted that compared with placebo, glycine was reduced by 0.95 standard deviation (SD) units after 1 year of estrogen therapy (95% CI, –1.09 to –0.8) and by 1.05 SD units after 1 year of estrogen plus progesterone therapy (95% CI, –1.22 to –0.88), which meant that this metabolite “had the largest decrease due to active HT.” The researchers further noted that among women receiving estrogen plus progesterone, those aged 70 to 79 years exhibited the strongest association between metabolites and HT, followed by those aged 60 to 69 years, with the weakest association found among those aged 50 to 59 years.

“We don’t use [hormone therapy] for primary prevention of diabetes, but there is a lot of data showing less of a progression to type 2 diabetes in women who take hormone therapy,” Hirsch said. “When I’m sitting with a patient who may have the beginning of prediabetes and she has some moderate symptoms of menopause, we might want to think about using hormone replacement therapy because of the data we have showing a less progression to diabetes.” – by Phil Neuffer


Hirsch H, et al. Abstract P-24. Presented at: North American Menopause Society Annual Meeting; Sept. 25-28, 2019; Chicago.

For more information:

Heather Hirsch, MD, can be reached at

Disclosure: Hirsch reports no relevant financial disclosures.