Injectable

(Updated June 2014)

Description

Depo-Provera^® (depot medroxyprogesterone acetate, or DMPA) is a progestin-only method. It is a 3-month injectable that delivers either 104 mg (in the subcutaneous formulation) or 150 mg (in the intramuscular formulation) of medroxyprogesterone acetate to inhibit ovulation. DMPA is a good contraceptive choice for women who cannot use estrogen.

Use

A provider administers the DMPA injection to the patient

subcutaneously or intramuscularly every 3 months. DMPA can be administered up to 2 weeks early or 2 weeks late (i.e., 10 to 14 weeks after the last injection) without the need for a protective back-up contraceptive method. If it is more than 2 weeks late, the injection can be administered if the woman is reasonably certain that she is not pregnant. Additional contraceptive protection should be used for the next 7 days.³⁹

Effectiveness

This method is very effective.⁴⁰ The failure rate with perfect use is 0.2 percent and with typical use is 6 percent.¹⁹ The convenience and high efficacy rate of DMPA have made this contraceptive method increasingly popular with teens.⁴¹

Risks

Effects on bone (see box)

Dispelling Myths About DMPA and Bone Health

In 2004, the FDA approved a “black box” warning regarding use of DMPA and loss of bone mineral density, based on clinical data showing a significant loss of BMD among women using DMPA.⁴² Ample research evidence suggests that the effects of DMPA on bone health may be less concerning that originally believed.
Premenopausal women who use DMPA for up to 5 years experience BMD loss similar to that associated with breastfeeding, and the loss is substantially reversed after cessation of DMPA.⁴³
The reliance on surrogate markers of bone loss may have heightened the concern about the effects of DMPA on bone; use of a surrogate endpoint (i.e., BMD) rather than a clinical endpoint (i.e., fracture) may have led to an inaccurate or overestimated assessment of the risks associated with DMPA.⁴⁴
Longer-term studies suggest that BMD may not be as affected by DMPA as suggested in studies of shorter duration. A 3-year observational study of established DMPA users > age 35 years (i.e., women who had attained peak bone mass) found that despite increased levels of bone turnover markers, BMD was not reduced in the hip or spine.⁴⁵
Experts have called for removal of the black box warning.
The American Congress of Obstetricians and Gynecologists (ACOG) and the World Health Organization support long-term contraceptive use of DMPA for women 18–45 years old.⁴⁶
In an opinion published in October 2008, ACOG recommended that clinicians not allow concerns about the effects of DMPA on BMD to prevent their prescribing the contraceptive or limit use to 2 years.⁴⁷ Instead, clinicians should inform women about the relative benefits and risks so they can weigh the risk of fracture with the risk of unintended pregnancy. The opinion piece noted that the reduction in BMD associated with DMPA use is similar to that seen during pregnancy and breastfeeding (approximately 3 to 5 percent per year).
Data on the effects of DMPA on bone health in individuals who have not yet attained peak bone health are not clear. The use of DMPA is designated category 1 or 2 for adolescents and perimenopausal women.⁵

Side Effects

Side effects include weight gain and menstrual cycle changes. Nearly all women experience alterations in the menstrual cycle—irregular bleeding, spotting, or rarely, heavy bleeding. After 6 months, fewer women experience excessive or frequent bleeding, and more women experience amenorrhea. By 1 year, up to 70 percent of women have amenorrhea.⁴⁸

Contraindications and Precautions

Medical Eligibility Criteria for DMPA
Category 4 (unacceptable health risk if the contraceptive method is used)	Current breast cancer
Category 3 (theoretical or proven risks usually outweigh the advantages of using the method)	Multiple risk factors for arterial cardiovascular disease (such as older age, smoking, diabetes, and hypertension) Hypertension (systolic >160 mm Hg or diastolic >100 mm Hg) Vascular disease Ischemic heart disease or stroke (current or history of)—for initiating or continuing method SLE (positive for antiphospholipid antibodies or status unknown; or if severe thrombocytopenia) Rheumatoid arthritis (designated category 2 if not on long-term corticosteroid treatment with a history of or risk factors for non-traumatic fractures) Migraine with aura—for continuing method (i.e., if migraines worsen in a woman who is already using DMPA) Unexplained vaginal bleeding prior to evaluation Breast cancer in past; no evidence of disease for 5 years Diabetes (only if nephropathy, retinopathy, neuropathy, or other vascular disease is present, or the duration of diabetes is >20 years) Severe cirrhosis Malignant liver tumor Certain antiretroviral and anticonvulsant medications (some are designated category 2)
Source: Reference 5

Advantages

Convenient, requires only four shots per year
Discreet
Very effective
Reversible
Amenorrhea (may improve conditions such as menorrhagia, dysmenorrhea, and iron deficiency anemia); may be a desired lifestyle change; can also decrease the risk of dysfunctional menstrual bleeding in women who are overweight
Lack of estrogen in DMPA makes it appropriate for smokers older than age 35, postpartum breastfeeding women, and others who have contraindications to estrogen
Reduces the risk of endometrial cancer by up to 80 percent, with continuing protection after discontinuation⁴⁹
Reduces risk of PID ⁵⁰ and uterine leiomyomata⁵¹
Can decrease the number and severity of crises in patients who have sickle cell anemia⁵²
Can decrease frequency of seizures and does not interact with anti-epileptic medications⁵³

Disadvantages

Requires visit to clinician for quarterly injection
Initial irregular bleeding
Weight gain may occur in some women due to increased appetite, particularly those who are sedentary or overweight when they begin to use DMPA⁵⁴ (Weight gain of 5 percent or more in the first 6 months of use may signal risk of continued weight increase while on DMPA⁵⁵)
Short-term, reversible BMD loss
Delayed return to fertility: the median time to conception for those who do conceive is 10 months after the last injection, much longer than with other hormonal methods
No protection against STIs

Counseling Messages

Bleeding profile improves over time; amenorrhea, which occurs in about half of users after 1 year of use, may be an advantage or disadvantage, depending on the woman.⁵⁶
It is important to consider genetic and lifestyle factors that contribute to osteoporosis when weighing the benefits and risks of DMPA.
It is important to promote bone health with weight-bearing exercise, intake of calcium and vitamin D, avoidance of tobacco, and limits on alcohol.
Non-hormonal back-up contraception is needed for the first 7 days.
This method does not protect against STIs.
The CDC updated its recommendations in 2012 to indicate that data are inconclusive as to whether women using DMPA might be at increased risk for HIV acquisition, and that these women should be strongly advised to always also use either female or male condoms and take other HIV prevention measures.⁵⁷

About Audrey Kelly, PharmD

Drug Integrity Associate Audrey Amos is a pharmacist with experience in health communication and has a passion for making health information accessible. She received her Doctor of Pharmacy degree from Butler University. As a Drug Integrity Associate, she audits drug content, addresses drug-related queries