Why Low Estrogen Drives Weight Gain in CFS & Fibromyalgia

Earlier in-house research at our Kona Research Center found that people with CFS and fibromyalgia experienced an average weight gain of 32½ pounds. This increase is influenced by several contributing factors, including:

1. Decreased energy production
2. Hormonal deficiencies, including low thyroid and low reproductive hormones
3. Fluctuating leptin levels causing increased appetite and inflammation
4. Decreased physical activity

Recently, the FDA has finally caught up to what I’ve been saying for decades. Research now confirms that hormone replacement therapy with estrogen and progesterone can be safe. What’s missing from much of the conversation is the essential detail that this safety applies to bioidentical hormones, not synthetic versions of estrogen and progesterone.

Estrogen deficiency doesn’t just accompany weight gain—it actively contributes to it. In a recent study, menopausal individuals taking GLP-1 medications (like tirzepatide or semaglutide) lost 28% more weight when estrogen and progesterone were part of their treatment, compared with those who were not receiving hormone support.

As women move through perimenopause, particularly those with fibromyalgia, hormonal shifts can do more than worsen pain and fatigue. They often trigger fibromyalgia flares and promote weight gain at the same time. In this group, I’ve found bioidentical hormone replacement to be especially helpful in addressing both symptom flares and metabolic changes.

I’ve found that a compounded vaginal cream containing BiEst (2.5 mg), progesterone (30 mg), and a small amount of testosterone (½ mg) often works best. In women over age 45, this approach can be especially helpful, not only for hormone balance but also for fibromyalgia symptoms overall. Supporting this, research by Professor Hillary White at Dartmouth College showed that low-dose topical testosterone reduced fibromyalgia pain—even in women whose testosterone levels were considered “normal.”

These compounded options are not typically covered by insurance. However, there are effective insurance-covered alternatives, including bioidentical estrogen patches (all currently available patches are bioidentical) paired with Prometrium® 100 mg capsules or a generic equivalent (bioidentical progesterone).

When progesterone is taken orally, I typically use 100–200 mg at bedtime, and in cases where anxiety or poor sleep are significant concerns, doses of up to 200 mg twice daily may be helpful. In some individuals, the higher doses can also improve pain and other symptoms. Progesterone acts much like the body’s natural calming agent, often described as nature’s version of Valium.