Hormone Therapy Reduced Insulin Resistance in Healthy Postmenopausal Women

CHICAGO — Hormone therapy for menopause symptoms reduced insulin resistance in healthy postmenopausal women, a systematic review and meta-analysis of 23 randomized trials showed.

Insulin resistance, measured by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), which uses fasting glucose and insulin levels, was significantly reduced in a pooled hormone therapy group compared with a placebo group, with a difference in means of -0.239 (95% CI -0.362 to -0.116, P<0.001), reported Tanya Li, BS, of the Drexel University College of Medicine in Philadelphia, at the Menopause Society annual meeting.

When types of hormone therapy were analyzed separately, both estrogen alone and combined estrogen and progestogen reduced insulin resistance, with a difference in means of -0.42 (P<0.001) and -0.14 (P=0.005) on the HOMA-IR measure, respectively.

“Overall, our findings can be used in a clinical setting when prescribing healthy postmenopausal woman hormone therapy and understanding its possible effects on insulin response as well,” Li said. “I think our findings can also help reassure the younger postmenopausal population that hormone therapy is indeed safe and effective.”

Menopause is associated with an increased risk of insulin resistance, which in turn can lead to metabolic consequences, including hyperglycemia, dyslipidemia, and hypertension, as well as diabetes and cardiometabolic diseases.

Previous meta-analyses have focused on the glycemic effects of hormone therapy in diabetic postmenopausal women, Li said, so she and her colleagues chose to focus on “healthy” postmenopausal women.

Monica De Paoli, MD, PhD, of McMaster University in Hamilton, Ontario, who was not involved in the study, told MedPage Today that “the idea here is that before menopause, we have estrogen and progesterone, and based on their fluctuations, we have our hormone cycle, so the idea here would be to sort of keep those hormone levels up to a certain point.”

De Paoli touched on recent efforts to alleviate concerns about taking hormone therapies, and to increase clinical awareness around their use. “Studies like this show that there are — in addition to treating the symptoms of menopause — additional benefits of hormone therapy, including reducing insulin resistance.”

Still, she said more basic research to establish mechanisms of action must be conducted. “This is such an understudied and poorly understood area, because we don’t have much data to this day to understand the different hormone compositions,” she noted.

“The clinician should start monitoring women throughout their lifespan” to see how their cardiometabolic indicators change throughout perimenopause and menopause, to tailor therapies accordingly, De Paoli added.

Li explained that possible explanations for the reduction in insulin resistance could be estrogen’s ability to improve insulin sensitivity in muscle and fat, helping cells respond better to it. It can also reduce visceral fat, which is more closely associated with insulin resistance. In addition, estrogen is an anti-inflammatory, and may lower levels of circulating free fatty acids.

For this systematic review and meta-analysis, the researchers used PubMed, Embase, and Medline to identify 23 eligible randomized controlled studies from 1998 to 2024. Participants could not have diabetes, hypertension, or cardiovascular disease at baseline. Insulin resistance values were measured at baseline and at the end of treatment.

In total, 5,553 participants were in the estrogen-alone group, 9,797 were in the combined estrogen and progestogen group, and 13,937 were in the placebo group. Mean patient age ranged from 47 to 75 years, and treatment duration ranged from 8 weeks to 2 years.

Estrogen formulations included oral conjugated equine estrogen and 17β-estradiol (oral or transdermal). Progestogen formulations included largely medroxyprogesterone acetate and norethisterone acetate.

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