Safety · Label read 2026-08-03
Progesterone side effects, and the caveat nobody prints
The rates below come from the Prometrium (progesterone, USP) capsules label, a three-year placebo-controlled trial. Two things almost every page quoting them leaves out: what the placebo arm did, and the fact that the trial arm was Prometrium 200 mg with conjugated estrogens 0.625 mg, not progesterone by itself. Both change what the numbers mean.
What is micronized progesterone?
Micronized progesterone is a form of the hormone progesterone ground into very small particles so the body can absorb it when swallowed, sold in the United States under the brand name Prometrium and as generics. In a standard menopause regimen its job is endometrial protection: taking estrogen alone thickens the lining of the uterus, and progesterone opposes that effect, which is why it is prescribed to women who still have a uterus. Micronized progesterone and synthetic progestins such as medroxyprogesterone are not the same class of drug, and the distinction matters, because most of what people believe about progestin risk comes from trials that used a synthetic.
Compounded progesterone creams, which several telehealth platforms dispense, are not FDA-approved products and have no adverse-reaction table of the kind below. What bioidentical actually means.
The label table, with the placebo column
| Reaction | Progesterone 200 mg + conjugated estrogens 0.625 mgn=178 | Placebon=174 |
|---|---|---|
| Headache | 31% | 27% |
| Breast tenderness | 27% | 6% |
| Joint pain | 20% | 29% |
| Depression | 19% | 12% |
| Dizziness | 15% | 9% |
| Abdominal bloating | 12% | 5% |
| Hot flashes | 11% | 35% |
| Urinary problems | 11% | 9% |
| Abdominal pain | 10% | 10% |
| Vaginal discharge | 10% | 3% |
| Nausea or vomiting | 8% | 7% |
| Chest pain | 7% | 5% |
| Night sweats | 7% | 17% |
| Breast pain | 6% | 2% |
| Swelling of hands and feet | 6% | 9% |
| Vaginal dryness | 6% | 10% |
| Constipation | 3% | 2% |
Reactions reported at 2% or more over three years. The label's table title cites a 875-patient trial; the two arms it reports are 178 and 174. Four rows are higher on placebo than on treatment: joint pain, swelling of hands and feet, vaginal dryness and hot flashes. That is what a placebo column is for.
Compounded progesterone has no table like this
Of the 13 women's-wing providers we track, 5 route you to FDA-approved progesterone (Alloy, Sesame Care, Hone Health, Hers Menopause, Wisp) and 3 dispense a compounded version (Winona, Gala Health, Telos RX).
That is not an accusation about safety. It is a statement about what evidence exists. A compounded preparation is mixed by a pharmacy and is not FDA-approved, so it never runs the registration trial that produces a table like the one above. If you are handed a compounded progesterone cream, there is no placebo-controlled rate to compare it against, because nobody measured one. Whether a provider tells you that before you buy is exactly what our Transparency Grade measures.
One label has dropped its boxed warning and one has not
The FDA announced removal of the boxed warnings from systemic menopause hormone therapy in November 2025 and approved the labelling changes in February 2026. Manufacturers update their posted labels on their own schedule, so the rollout is uneven right now, and you can see it in the structured label data.
We counted LOINC section code 34066-1, the SPL code for a boxed warning, in each label on 2026-08-03. The Prometrium (progesterone, USP) capsules label, effective 2026-07-23, contains no boxed warning section. The Vivelle-Dot (estradiol transdermal system) label, revised 11/2023, still contains one. Same therapy class, two manufacturers, one updated and one not. The Vivelle result is the control: it shows the check detects the section where it exists, so the absence on Prometrium is a finding rather than a failed read. What the FDA actually changed.
FAQ
Progesterone side effects, answered
What are the side effects of micronized progesterone?
On the Prometrium (progesterone, USP) capsules label, the reactions reported at 2% or more over three years were headache (31%), breast tenderness (27%), joint pain (20%), depression (19%), dizziness (15%), abdominal bloating (12%), hot flashes (11%), urinary problems (11%), abdominal pain (10%) and vaginal discharge (10%). The critical caveat, which almost no consumer page prints: that table is Prometrium 200 mg with conjugated estrogens 0.625 mg, not progesterone on its own, measured against placebo (n=178 against n=174). For several rows the placebo arm was higher, including joint pain at 29% and vaginal dryness at 10%. Micronized progesterone also carries a warning about drowsiness, which is why it is usually taken at bedtime.
Does progesterone reduce hot flashes?
The label table cannot answer that, and reading it as if it can is the most common error on this topic. Hot flashes appear at 11% on the combined regimen against 35% on placebo, but the regimen includes conjugated estrogens 0.625 mg, and estrogen is the established treatment for vasomotor symptoms. Attributing that difference to the progesterone component is not supported by this trial design. Progesterone's role in a standard regimen is endometrial protection for a woman with a uterus taking estrogen, not symptom relief in its own right.
Is compounded progesterone cream the same as Prometrium?
No, and the difference is checkable. FDA-approved micronized progesterone has a placebo-controlled adverse-reaction table because it ran a registration trial. A compounded progesterone cream has none, because compounded preparations are not FDA-approved and do not run those trials. Of the 13 women's-wing providers we track, 3 dispense compounded progesterone (Winona, Gala Health, Telos RX). That is not a safety accusation, it is a statement about what evidence exists: for the compounded version there is no rate to compare against placebo, because nobody measured one.
Does progesterone cause weight gain?
Weight gain does not appear at all in the Prometrium three-year adverse-reaction table, which lists every reaction reported at 2% or more. Abdominal bloating does, at 12% on the combined regimen against 5% on placebo, and bloating is frequently reported as weight gain. On the estradiol patch label the same pattern holds: weight increase shows no dose-response and reaches 0% at the highest dose.
Sources
- Prometrium (progesterone, USP) capsules prescribing information, Acertis Pharmaceuticals, LLC, DailyMed (SPL effective 2026-07-23, read 2026-08-03 from the structured XML). Table 7 is the source for every rate on this page.
- FDA, human drug compounding
- FDA, approved labeling changes for menopausal hormone therapy products
- The Menopause Society, 2022 hormone therapy position statement (PMID 35797481)
This is general information, not medical advice. Progesterone is a prescription medicine and whether you need it, at which dose and in which form, is a decision for you and a licensed clinician. Reviewed by Iacob Pastina.
Gala Health
Sesame Care
Wisp