ESTROGEN OR NO ESTROGEN; THAT’S THE MENOPAUSAL QUESTION!
The Women’s Health Initiative (WHI) probably had the most profound effect on the treatment of menopause than any other single event in medical history. Menopause is the natural process in which women in their late 40’s and 50’s experience the multiple symptoms of ovarian failure and the decreased production of estrogen. Prior to July 2002, the standard of care was ERT, estrogen replacement therapy (also called hormone replacement therapy-HRT). The theory being, if the ovary couldn’t provide adequate estrogen, the doctor could in the form of estrogen shots, pills, patches, or whatever, to stop the annoying hot flashes, vaginal dryness, mood swings, depression, insulin resistance, and weight gain.
It was in July 2002 that the hormone therapy trials of the WHI were stopped because menopausal women taking combined estrogen and progesterone were found to be at increased risk of breast cancer, heart attacks, and strokes. Then, in March 2004, those women taking estrogen alone were found to be at increased risk of strokes. These two events had the profound effect of completely eliminating any hormone or estrogen replacement therapy. The risks of treatment were greater than the symptoms of menopause. HRT was relegated to the scrap heap, and estrogen became persona non grata. Women everywhere were taken off estrogen causing widespread anxiety and symptoms that were uncontrollable, and doctors were fearful of litigation. For the next several years, patients and physicians were adrift and directionless, not knowing what to do about the symptoms driving them crazy.
The lack of naturally-produced estrogen posed a real problem for menopausal women, and weight gain became a big issue. Emotional swings led to overeating, and coping became more difficult. Finally, after mountains of evidence, and a thorough re-evaluation of HRT, the complaints of millions of women were heard. It was decided post menopausal women with no history of blood clots, stroke, or breast cancer were safe to resume taking estrogen. That helped to ease mood swings, hot flashes, etc. but issue of weight gain was not solved. Enter GLP-1 semaglutide (Ozempic, Wegovy, Rybelsus).
In postmenopausal women, the addition of semaglutide to estrogen (or HRT) achieved “greater weight loss” than either drug alone. This combination plus proper nutritional support not only reduces weight, but protects women from muscle and bone loss. Adequate protein and reduced carbohydrates decrease the risk of postmenopausal weight gain.
Dr. G’s Opinion: Stopping HRT was a disaster for postmenopausal women. Restarting it in women with no risk factors restored their quality of life. Adding GLP-1 receptor agonists to estrogen achieves the desired effect without increasing the risks to women. This combination stabilized emotional problems and overeating, helped with coping skills, gave women the ability to deal with an aging body, and improved self-image. The return of estrogen has not seen the devastating effects that were once greatly feared. We know GLP-1’s work so the future for postmenopausal women has a new, more positive direction.
Reference: Larkin M. Hormones, Menopause, and Weight Loss: What to Tell Patients. Medscape 2025 October 15. www.medscape.com/viewarticle/hormones-menopause-
