MEDROXYPROGESTERONE ACETATE
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Medroxyprogesterone acetate is a progestin that binds to progesterone receptors, inhibiting gonadotropin secretion (LH, FSH) from the pituitary, thereby suppressing ovulation and altering the endometrial lining.
| Metabolism | Hepatic metabolism via CYP3A4; undergoes hydroxylation and conjugation. Metabolites are excreted primarily in urine and feces. |
| Excretion | Primarily metabolized in the liver; metabolites are excreted in urine (50-70%) and feces (30-50%). Less than 5% excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 12-17 hours after oral administration; with depot intramuscular injection, the half-life is prolonged (up to 50-60 days due to slow release from injection site). |
| Protein binding | 86-99% bound primarily to albumin, with a smaller fraction bound to sex hormone-binding globulin (SHBG). |
| Volume of Distribution | Apparent volume of distribution is approximately 0.5-1.2 L/kg, indicating extensive distribution into tissues. |
| Bioavailability | Oral: 100%? (complete absorption but extensive first-pass metabolism reduces systemic bioavailability to ~3-10%); Intramuscular: 100% bioavailability (bypasses first-pass metabolism). |
| Onset of Action | Oral: 1-2 hours for hormonal effects; Intramuscular (depot): within 24-72 hours for contraceptive effect; onset of amenorrhea may take 1-2 cycles. |
| Duration of Action | Contraceptive effect: 14 weeks after a single 150 mg IM injection; oral: duration of action is 24 hours for hormonal effects; therapeutic effects for endometriosis: 3-6 months after depo injection. |
150 mg IM every 3 months for contraception; 400-1000 mg IM weekly for endometrial cancer; 5-10 mg PO daily for secondary amenorrhea.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment. Not removed by dialysis. |
| Liver impairment | Contraindicated in severe hepatic disease (Child-Pugh class C). Use with caution in mild to moderate impairment; consider dose reduction. |
| Pediatric use | Not indicated for use in pediatric patients for contraception; off-label use for precocious puberty: 100-150 mg IM every 2-4 weeks. |
| Geriatric use | No specific dose adjustment; use lowest effective dose due to potential for decreased renal/hepatic function and increased sensitivity to side effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CYP3A4 inducers can decrease efficacy Can cause thromboembolic disorders.
| Breastfeeding | Excreted in breast milk in small amounts; estimated relative infant dose <10% of maternal weight-adjusted dose. M/P ratio approximately 0.7-1.0. Considered compatible with breastfeeding by AAP and WHO, but monitor infant for jaundice or hormonal effects. |
| Teratogenic Risk | First trimester: Not recommended due to potential for genital abnormalities in male fetuses (hypospadias) and cardiovascular/limb defects, though data are conflicting. Second/third trimesters: No known increased risk of congenital anomalies; high doses may cause transient neonatal effects such as jaundice or electrolyte disturbances. |
■ FDA Black Box Warning
Risk of significant bone mineral density loss with long-term use; loss is greater with increasing duration and may not be completely reversible.
| Common Effects | abnormal uterine bleeding |
| Serious Effects |
Known or suspected pregnancy, undiagnosed vaginal bleeding, breast cancer, thromboembolic disorders, liver disease or tumors, hypersensitivity to medroxyprogesterone acetate.
| Precautions | Thromboembolic disorders, cardiovascular disease risk, bone mineral density loss, depression, fluid retention, hepatic impairment, glucose intolerance, and risk of ectopic pregnancy (if used for contraception and fails). |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure, blood glucose, and liver function tests. Fetal ultrasound to assess growth and anatomy. In prolonged use (e.g., for contraception during lactation), assess bone density in mother. No specific fetal monitoring required for short-term use. |
| Fertility Effects | May delay return of ovulation after discontinuation; average delay 4-6 months with depot formulations. Reversible; no permanent impact on fertility. |