Short answer: In the label's 10-week ART study of 808 women, the most common Endometrin side effects were pain after egg retrieval (28% on 100 mg twice daily, 25% three times daily), abdominal pain (12% each), nausea (8% and 7%) and ovarian hyperstimulation syndrome (7% each). The study had no placebo group. Warnings cover blood clots and depression. There is no boxed warning.
What Endometrin is approved for: Endometrin is a progesterone vaginal insert approved, as part of an Assisted Reproductive Technology (ART) program, to support embryo implantation in infertile women under 35 by supplementing corpus luteum function, and to maintain pregnancy after implantation up to 10 weeks (section 1). Efficacy in women 35 and older has not been clearly established (section 2).
Source
ENDOMETRIN (progesterone) vaginal insert, prescribing information and Patient Information. Ferring Pharmaceuticals. DailyMed, version published August 5, 2026. DailyMed setid 2ba50fa9-b349-40cb-9a4b-1af8faa4ec09
No. The current Endometrin label has no boxed warning.
These are the label's own numbers from the Adverse Reactions section. Where the label compares with placebo (a dummy treatment), both columns are shown, so you can see how much more often a reaction happened on Endometrin.
| Adverse reaction | Endometrin 100 mg twice daily (N=404) | Endometrin 100 mg three times daily (N=404) |
|---|---|---|
| Post-oocyte retrieval pain | 115 (28%) | 102 (25%) |
| Abdominal pain | 50 (12%) | 50 (12%) |
| Nausea | 32 (8%) | 29 (7%) |
| Ovarian hyperstimulation syndrome | 30 (7%) | 27 (7%) |
| Abdominal distension | 18 (4%) | 17 (4%) |
| Headache | 15 (4%) | 13 (3%) |
| Uterine spasm | 15 (4%) | 11 (3%) |
| Vaginal bleeding | 13 (3%) | 14 (3%) |
| Vomiting | 13 (3%) | 9 (2%) |
| Urinary tract infection | 9 (2%) | 4 (1%) |
| Constipation | 9 (2%) | 14 (3%) |
| Fatigue | 7 (2%) | 12 (3%) |
Adverse reactions at 2% or more in either Endometrin group over 10 weeks. The study compared Endometrin with a vaginal active comparator, not placebo. Values are number of women (percent).
Less common reactions on Endometrin included vaginal irritation, itching, burning and discomfort, hives and swelling of the legs or arms (peripheral edema).
Reactions reported with other progesterone products include breast tenderness, bloating, mood swings, irritability and drowsiness.
Twice daily: 143 of 404 women (35%) had live births, 13 (3%) spontaneous abortions and 1 (0.2%) ectopic pregnancy; birth defects in 7 infants (3% of 203 live births). Three times daily: 155 (38%) live births, 22 (5%) spontaneous abortions, 4 (1%) ectopic pregnancies; birth defects in 7 infants (3% of 223 live births).
The label notes the US background risk of major birth defects and miscarriage in recognized pregnancies is 2% to 4% and 15% to 20%.
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Who should not use it. Women with prior allergy to progesterone or the ingredients, undiagnosed abnormal vaginal bleeding, a known missed abortion or ectopic pregnancy, liver adenoma, liver cancer, acute hepatitis or severe cirrhosis, current or past hormone-sensitive cancer such as breast cancer, or active or past arterial or venous blood clots or severe thrombophlebitis.
Heart attack, stroke and blood clots. Life-threatening arterial or venous clotting disorders may occur during hormone treatment, including Endometrin. Providers watch for early signs of heart attack, stroke, blood clots, thrombophlebitis or retinal thrombosis, and Endometrin is stopped if any is suspected.
Depression. Women with a history of depression are closely observed, and stopping Endometrin is considered if symptoms worsen.
Other vaginal products and CYP3A4 inducers. Endometrin is not recommended with other vaginal products, such as antifungals, which may change progesterone release and absorption. Medicines that induce the liver enzyme CYP3A4 may lower progesterone levels and reduce efficacy.
Age and body weight. Endometrin is not indicated for women 65 and older. Safety and efficacy in women with a BMI over 34 kg/m2 have not been studied (section 8.6).
From the Patient Information that comes with Endometrin:
Dose Track has a side-effect log. Each entry records the symptom, a severity (none, mild, moderate, severe or life-threatening), the date and an optional note, and can be tied to a specific dose or logged on its own. The history screen shows what you logged over time, which makes it easier to tell your prescriber when a reaction started and whether it is easing. The app records what you enter; it does not judge whether a symptom is serious. For anything on the label's call-your-doctor list, call your doctor.
This page is what the FDA label says, in plain words. It is not medical advice. Follow your prescriber, and ask them or your pharmacist about anything here.