Contraceptive injections (medroxyprogesterone)

Contraceptive Injections: Medroxyprogesterone Acetate (DMPA)

Medroxyprogesterone acetate (DMPA) is a long-acting progestin-only contraceptive administered via intramuscular (IM) or subcutaneous (SC) injection. It is commonly used under the brand names Depo-Provera (intramuscular formulation) and Sayana Press or Depo-SubQ Provera 104 (subcutaneous formulations). As a depot preparation, it provides extended contraception lasting approximately three months (12–13 weeks) per dose. Its widespread use is attributed to its convenience, efficacy, and non-estrogenic profile, making it suitable for patients who cannot tolerate estrogen.

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1. Formulations and Administration

A. Intramuscular (IM)

• Product Name: Depo-Provera

• Dose: 150 mg medroxyprogesterone acetate

• Route: Deep intramuscular injection (e.g., gluteal or deltoid muscle)

• Interval: Every 12 weeks (84 days)

B. Subcutaneous (SC)

• Product Name: Depo-SubQ Provera 104 or Sayana Press

• Dose: 104 mg medroxyprogesterone acetate

• Route: Subcutaneous injection (abdomen or thigh; Sayana Press allows self-injection)

• Interval: Every 12 to 14 weeks

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2. Mechanism of Action

Medroxyprogesterone acetate provides contraception through multiple mechanisms, all of which act synergistically to prevent pregnancy:

• Inhibits ovulation by suppressing the mid-cycle luteinizing hormone (LH) surge

• Thickens cervical mucus, creating a barrier that prevents sperm from reaching the ovum

• Induces endometrial atrophy, making the uterine lining unsuitable for implantation

The hypothalamic-pituitary-ovarian axis is profoundly suppressed, resulting in anovulation for the duration of the drug's efficacy.

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3. Efficacy

• Perfect use failure rate: 0.2% per year

• Typical use failure rate: ~4% per year (primarily due to delays in reinjection)

• DMPA is highly effective with proper adherence to the 12-week dosing schedule.

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4. Indications

• Contraception in women seeking long-acting birth control

• Contraindicated or intolerant to estrogen (e.g., migraines with aura, smokers >35 years)

• Women who prefer non-daily, non-invasive contraception

• Menstrual disorders (e.g., heavy menstrual bleeding, dysmenorrhea)

• Endometriosis-associated pain

• Fibroid-related bleeding

• Adolescents and postpartum women, including breastfeeding women

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5. Dosage and Timing

A. Initiation

• First 5 days of the menstrual cycle: no backup contraception needed

• Postpartum (non-breastfeeding): within 5 days postpartum

• Postpartum (breastfeeding): ≥6 weeks postpartum recommended

• After abortion/miscarriage: within 5 days for immediate protection

B. Late Injection Window

• Up to 15 weeks (105 days) is generally acceptable for a reinjection

• If >15 weeks, rule out pregnancy and advise backup contraception for 7 days post-injection

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6. Advantages

• Highly effective and long-acting (3 months per dose)

• Estrogen-free (safe for patients with estrogen contraindications)

• Reduces:

  • Menstrual bleeding

  • Menstrual cramps

  • Ovulation pain

• May induce amenorrhea in up to 50% of women after 1 year

• Reduces risk of:

  • Endometrial cancer

  • Iron-deficiency anemia

  • Ectopic pregnancy

  • Seizures in women with epilepsy

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7. Disadvantages and Side Effects

A. Common Side Effects

• Menstrual irregularities: spotting, prolonged bleeding, or amenorrhea

• Weight gain: average 2–5 kg after 1 year; may increase further

• Mood changes: depression, irritability

• Decreased libido

• Delayed return to fertility: average 9–10 months from the last injection

• Acne or skin changes

• Headaches

• Hair loss

B. Long-Term Side Effects

• Bone mineral density (BMD) reduction: especially in adolescents and long-term users; typically reversible upon discontinuation

• FDA advises limiting use to 2 years unless no alternatives are suitable

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8. Contraindications

• Known or suspected pregnancy

• Active thromboembolic disorders

• Liver disease (severe impairment, hepatic tumors)

• Unexplained vaginal bleeding

• Known breast cancer or history of hormone-sensitive malignancies

• Hypersensitivity to medroxyprogesterone acetate or any component

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9. Warnings and Precautions

• Osteoporosis: BMD monitoring is recommended in long-term use (especially adolescents)

• Depression history: caution in patients with mood disorders

• Diabetes mellitus: may affect glucose tolerance

• Hypertension: monitor blood pressure regularly

• Weight gain risk: more pronounced in obese individuals at baseline

• Injection site reactions: especially with subcutaneous formulation

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10. Fertility After Discontinuation

• Delayed return to ovulation:

  • Average 10 months from last injection

  • Some women may take up to 18 months

• Not suitable for women planning pregnancy in the near future

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11. Use in Special Populations

A. Adolescents

• Effective contraception

• Increased concern about bone loss

• Weigh benefits vs. skeletal impact; supplement calcium and vitamin D

B. Postpartum/Breastfeeding Women

• Safe in lactating women: does not affect milk quantity/quality

• Initiation at ≥6 weeks postpartum minimizes theoretical neonatal exposure

C. Perimenopausal Women

• May provide contraception and reduce perimenopausal bleeding

• Amenorrhea is common, which may mask menopause onset

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12. Drug Interactions

Medroxyprogesterone is not significantly affected by most cytochrome P450 enzyme inducers or inhibitors because it bypasses the liver via depot administration. However, the following are important:

• CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, efavirenz): minimal effect on efficacy due to depot action

• Corticosteroids: may augment fluid retention and affect glycemic control

• HIV antiretrovirals: no major interaction

• Anticoagulants: theoretical prothrombotic risk with progestins; data limited

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13. Comparative Overview

Aspect	Depo-Provera (IM)	Sayana Press (SC)
Dose	150 mg	104 mg
Route	Intramuscular	Subcutaneous
Self-administration	No	Yes (Sayana Press)
Injection interval	12 weeks	12–14 weeks
Common brand	Depo-Provera	Sayana Press, Depo-SubQ Provera 104

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14. Patient Counseling Points

• Administer every 12 weeks; do not exceed 15 weeks

• May take up to a year to become pregnant after stopping

• Menstrual changes (including no periods) are expected and usually not harmful

• Weight gain is possible; encourage healthy lifestyle

• Importance of calcium and vitamin D intake

• Seek medical attention if:

  • Heavy/prolonged bleeding

  • Severe depression

  • Suspected pregnancy

• Counsel on no protection against STIs – recommend condom use as needed

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15. Monitoring Recommendations

• Weight and BMI

• Menstrual bleeding patterns

• Mood and psychological well-being

• Bone density (especially in long-term users or adolescents)

• Blood pressure and blood glucose in at-risk patients

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16. Off-Label Uses and Non-Contraceptive Benefits

• Endometriosis-associated pain relief

• Uterine fibroids: reduces bleeding

• Anemia from heavy menstruation

• Pelvic inflammatory disease prevention (some evidence due to mucus thickening)

• Reduction in seizures in epileptic women due to hormone stabilization

• May provide protection against endometrial cancer