Short answer: In the label's IVF study of Crinone 8% once daily, common side effects were breast enlargement (40%), constipation (27%), somnolence (27%), nausea (22%), headache and perineal pain (17% each). In the donor egg study, cramps were 15% and headache and breast pain 13% each. These studies had no placebo group. The label warns about blood clots and has no boxed warning.
What Crinone is approved for: Crinone 8% is approved for progesterone supplementation or replacement as part of Assisted Reproductive Technology (ART) treatment for infertile women with progesterone deficiency. Crinone 4% is approved to treat secondary amenorrhea (periods that have stopped), and Crinone 8% is for women who did not respond to the 4% gel (Indications and Usage).
Source
CRINONE (progesterone gel) 4% and 8%, prescribing information, Patient Information and Instructions for Use. AbbVie (Allergan). DailyMed, version published May 20, 2026. DailyMed setid 75e97aa1-daa4-45f9-b2e2-1a371302914e
No. The current Crinone 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 Crinone.
| Adverse event | Crinone 8% once daily (n=139) |
|---|---|
| Breast enlargement | 40% |
| Constipation | 27% |
| Somnolence | 27% |
| Nausea | 22% |
| Headache | 17% |
| Perineal pain female | 17% |
| Nervousness | 16% |
| Nocturia | 13% |
| Abdominal pain | 12% |
| Depression | 11% |
| Libido decreased | 10% |
| Diarrhea | 8% |
| Arthralgia | 8% |
| Dyspareunia | 6% |
| Vomiting | 5% |
Luteal phase support during IVF, Crinone 8% once daily from within 24 hours of embryo transfer through Day 30. Open-label study with no placebo group. Values are percent of women.
| Adverse event | Crinone 8% twice daily (n=61) |
|---|---|
| Cramps | 15% |
| Headache | 13% |
| Breast pain | 13% |
| Pain | 8% |
| Bloating | 7% |
| Nausea | 7% |
| Vaginal discharge | 7% |
| Dizziness | 5% |
| Genital moniliasis (yeast infection) | 5% |
| Genital pruritus | 5% |
Women with ovarian failure undergoing donor oocyte transfer. Open-label study; values are percent of women.
| Adverse event | Estrogen + Crinone 4% (n=62) | Estrogen + Crinone 8% (n=65) |
|---|---|---|
| Cramps | 12 (19%) | 17 (26%) |
| Emotional lability | 14 (23%) | 14 (22%) |
| Fatigue | 13 (21%) | 14 (22%) |
| Headache | 12 (19%) | 10 (15%) |
| Depression | 12 (19%) | 10 (15%) |
| Sleep disorder | 11 (18%) | 12 (18%) |
| Bloating | 8 (13%) | 8 (12%) |
| Vaginal discharge | 7 (11%) | 2 (3%) |
| Abdominal pain | 3 (5%) | 6 (9%) |
| Nausea | 5 (8%) | 4 (6%) |
Secondary amenorrhea: 127 women on estrogen plus Crinone every other day for six doses. Values are number of women (percent).
Small, white globules may appear as a vaginal discharge, possibly from gel building up, even several days after use.
Donor egg study: clinical pregnancies in 26 of 54 women (48%); 7 had spontaneous abortions and 17 delivered 25 apparently normal newborns. IVF study: clinical pregnancies in 36 of 139 (26%); of 47 newborns, one had a teratoma with cleft palate and one respiratory distress syndrome.
Secondary amenorrhea: in cycle 2, Crinone 4% brought on bleeding in 79% of women and Crinone 8% in 77%.
Relative to intramuscular progesterone, bioavailability was 27.6% for Crinone 4% and 19.8% for Crinone 8%. Absorption half-life is about 25 to 50 hours.
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. People with known sensitivity to Crinone or its ingredients, undiagnosed vaginal bleeding, liver dysfunction or disease, known or suspected cancer of the breast or genital organs, a missed abortion, or active or past hormone-related blood clots or thrombophlebitis.
Blood clots. Prescribers watch for the earliest signs of clotting disorders, including thrombophlebitis, stroke, pulmonary embolism and retinal thrombosis. Crinone is stopped right away if any occurs or is suspected.
Recurrent miscarriage. Progesterone and progestins have been used to try to prevent miscarriage in women with recurrent pregnancy loss, but there is no adequate evidence that they work for this.
Exams and bleeding. The pre-treatment exam includes the breasts, pelvic organs and a Pap smear. Breakthrough or undiagnosed vaginal bleeding is investigated.
Fluid, mood and blood sugar. Progestogens can cause fluid retention, so epilepsy, migraine, asthma and heart or kidney problems are watched. People with past depression are observed and the drug is stopped if depression returns seriously. People with diabetes are watched because glucose tolerance can drop.
Other vaginal products. Crinone is not used at the same time as other vaginal treatments; if one is needed, it is used at least 6 hours before or after Crinone.
From the Patient Information that comes with Crinone:
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.