When should Depo-Provera (medroxyprogesterone acetate) be prescribed to a female patient of reproductive age for contraception?

When to Prescribe Depo-Provera

Depo-Provera should be prescribed to women of reproductive age seeking highly effective, long-acting reversible contraception who prefer a method that does not require daily adherence and who can accept menstrual irregularities as a common side effect. 1

Primary Indications for Prescribing

Contraceptive Efficacy

• Depo-Provera is indicated as a first-line contraceptive option for women seeking highly effective pregnancy prevention, with a failure rate of less than 1% per year with perfect use and approximately 6% with typical use. 1, 2
• The method is particularly valuable for women who have difficulty with daily pill-taking or who lead irregular lifestyles, as it eliminates the need for user-dependent daily adherence. 2

Ideal Candidate Characteristics

• Women who cannot tolerate estrogen-containing contraceptives due to contraindications such as hypertension, history of thromboembolism, or focal migraine. 2
• Women who experience excessive bleeding with intrauterine devices (IUDs) or cannot tolerate IUD-related pain. 3
• Postpartum women who wish to breastfeed, as Depo-Provera does not adversely affect lactation. 3
• Women in resource-limited settings where anemia and nutritional problems are prevalent, as Depo-Provera causes less bleeding than IUDs or oral contraceptives and does not suppress vitamin levels. 3

Timing of Initial Administration

First Injection Timing

• The first injection should be given ONLY during the first 5 days of a normal menstrual period to ensure the patient is not pregnant at the time of administration. 4
• Alternatively, the "quick start" or "mid-cycle" initiation is acceptable if the provider can be reasonably certain the patient is not pregnant using established criteria. 1, 5

Criteria for Reasonable Certainty of Non-Pregnancy

The provider can be reasonably certain a woman is not pregnant if she meets any one of the following: 5

• Is ≤7 days after the start of normal menses
• Has not had sexual intercourse since the start of last normal menses
• Has been using a reliable contraceptive method correctly and consistently
• Is ≤7 days after spontaneous or induced abortion
• Is within 4 weeks postpartum
• Is fully or nearly fully breastfeeding (≥85% of feeds are breastfeeds), amenorrheic, and <6 months postpartum

Postpartum Administration

• In postpartum mothers who exclusively breastfeed, administer Depo-Provera during or after the sixth postpartum week. 4
• For non-breastfeeding women, Depo-Provera can be started immediately postpartum. 5

Backup Contraception Requirements

• If Depo-Provera is started within the first 7 days of menses, no backup contraception is needed. 6
• If started more than 7 days after menses, patients must use backup contraception (condoms or abstinence) for 7 consecutive days after the injection. 1, 6

Pre-Administration Requirements

What is NOT Required Before Prescribing

A major advantage of Depo-Provera is that minimal pre-administration testing is required, which facilitates same-day initiation: 5, 6

• Pelvic examination is not required
• Cervical cytology (Pap smear) is not required
• Clinical breast examination is not required
• Laboratory tests for glucose, lipids, liver enzymes, hemoglobin, or thrombogenic mutations are not required
• HIV screening is not required
• Blood pressure measurement is not required for the injectable formulation (though it may be measured as part of routine care)

What IS Required

• Pregnancy must be ruled out using clinical criteria before the first injection. 4
• Comprehensive counseling about menstrual changes, weight gain potential, and bone mineral density effects is essential before initiation. 1, 2

Absolute Contraindications

Do not prescribe Depo-Provera in the following circumstances: 4, 7

• Known or suspected breast cancer or history of breast cancer
• Active thrombophlebitis, current or history of thromboembolic disorders, or cerebrovascular disease
• Significant liver disease or known liver impairment
• Undiagnosed vaginal bleeding
• Known hypersensitivity to medroxyprogesterone acetate or any ingredients
• History of stroke or myocardial infarction

Special Populations Requiring Caution

• Women with risk factors for osteoporosis (metabolic bone disease, chronic alcohol/tobacco use, anorexia nervosa, strong family history of osteoporosis, chronic use of anticonvulsants or corticosteroids) require careful risk-benefit assessment. 4
• Women with a strong family history of breast cancer should be monitored with particular care, though this is not an absolute contraindication. 4

Duration of Use Considerations

The 2-Year Recommendation

• The FDA label states that Depo-Provera is not recommended as a long-term (longer than 2 years) birth control method unless other options are considered inadequate, due to concerns about bone mineral density loss. 4
• However, the American College of Obstetricians and Gynecologists does not recommend limiting use to 2 years, as the benefits of pregnancy prevention generally outweigh the risks. 1, 7
• If a woman needs to continue using Depo-Provera long-term beyond 2 years, bone mineral density should be evaluated. 4

Bone Mineral Density Counseling

All patients should receive counseling on skeletal health promotion: 1

• Daily intake of calcium and vitamin D
• Regular weight-bearing exercise
• Avoidance of smoking and alcohol

Essential Pre-Injection Counseling

Menstrual Changes

• Nearly all patients experience menstrual irregularities initially with unpredictable spotting and bleeding. 1
• Bleeding patterns typically improve over time, with amenorrhea becoming common with continued use (often by 12 months). 1, 8
• Pre-injection counseling about menstrual changes significantly reduces discontinuation rates, making this counseling essential. 1

Weight Gain

• Weight gain occurs in some but not all patients. 1
• A significant predictor of future excessive weight gain is weight gain status at 6 months; patients gaining >5% of body weight at 6 months are at higher risk for continued weight gain. 1

Return to Fertility

• Patients must understand that return to fertility is delayed after discontinuation, with time to ovulation ranging from 15 to 49 weeks after the last injection. 1, 9
• MPA can be detected in serum for as long as 9 months after a single 150 mg injection. 9

STI Protection

• Patients must be counseled to use condoms at all times for STI protection, as Depo-Provera provides no protection against sexually transmitted infections. 1

Formulation Options

Two formulations are available with equivalent effectiveness: 1

• 150 mg intramuscularly every 13 weeks (91 days)
• 104 mg subcutaneously every 13 weeks (91 days)

The subcutaneous formulation can be self-administered as an off-label use when prescribed by a provider, with appropriate instruction on injection technique and sharps disposal. 1

Repeat Injection Schedule

• Schedule repeat injections every 13 weeks (91 days). 1
• Many providers schedule appointments every 11-12 weeks to allow buffer time for missed appointments. 1
• Injections can be given up to 2 weeks late (14 weeks from last injection) without requiring additional contraceptive protection. 1
• If more than 2 weeks late (>14 weeks), the patient can still receive the injection if reasonably certain she is not pregnant, but must use backup contraception for 7 days. 1

Common Pitfalls to Avoid

• Do not fail to counsel about menstrual irregularities before the first injection, as this significantly reduces discontinuation rates. 1
• Do not assume amenorrhea after Depo-Provera is pathologic without ruling out other causes. 1
• Do not routinely monitor bone density or limit use to 2 years based solely on BMD concerns in women without other risk factors, as the contraceptive benefits generally outweigh risks. 1, 7
• Do not delay prescribing Depo-Provera due to unnecessary pre-administration testing (pelvic exam, Pap smear, blood pressure, labs), as these are not required and create barriers to access. 5
• Do not prescribe Depo-Provera for short-term menstrual cycle planning; oral medroxyprogesterone acetate is the appropriate formulation for brief cycle manipulation in women with secondary amenorrhea. 6