Progestin Contraceptive Injections

(Depot Medroxyprogesterone Acetate)

ByFrances E. Casey, MD, MPH, Virginia Commonwealth University Medical Center
Reviewed/Revised Jul 2023
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    Various contraceptive progestin injections are available worldwide.

    With DMPA, pregnancy rates in the first year are 0.2% with perfect use and about 6% with typical use (ie, delays between injections).

    DMPA is available in two different formulations; it may be given as an IM (150 mg) or subcutaneous injection (104 mg) every 3 months. The injection site should not be massaged because doing so may increase the rate of absorption. Effective contraceptive hormonal serum levels are usually attained as early as 24 hours after injection and are maintained for at least 14 weeks although levels may be high enough to remain effective for up to 16 weeks.

    If the interval between injections is > 16 weeks, a pregnancy test should be done before the next injection is given. DMPA may be started immediately (a quick-start protocol) if DMPA is given within the first 5 to 7 days of the menstrual cycle. If it is not started during this time frame, a backup contraceptive method should be used concurrently for 7 days.

    DMPA may also be given immediately after a spontaneous or induced abortion or immediately postpartum regardless of breastfeeding status.

    Noristerat (NET-EN)

    Contraindications and adverse effects

    There are few contraindications for progestin injections, and these are similar to progestin-only oral contraceptives.

    The most common adverse effect of progestin injections is irregular vaginal bleeding. In the 3 months after the first injection, approximately 30% of users have amenorrhea. Another 30% have spotting or irregular bleeding (usually light) > 11 days per month. Despite these bleeding abnormalities, anemia does not usually result. With continued use, bleeding tends to decrease. After 2 years, approximately 70% of users have amenorrhea.

    Because DMPA has a long duration of action, ovulation may be delayed after the medication is discontinued. After the last injection, a regular menstrual cycle resumes in about half the women within 6 months and in about three fourths within 1 year. However, ovulation may be delayed for up to 18 months. After ovulation occurs, fertility is usually rapidly restored. For women using NET-EN, return to ovulation occurs more rapidly, with an average of 3 months, and return to fertility within 6 months (1).

    Women typically gain 1.5 to 4 kg during the first year of progestin injection use and continue to gain weight thereafter. Because changes in appetite rather than metabolism are thought to be responsible, women who want to use progestin injections are usually advised to limit caloric intake and increase energy expenditure.

    In some studies, 1 to 5% of women using DMPA reported depression or mood changes (2). However, baseline scoring before starting DMPA was not accounted for. In well-designed studies, no evidence of exacerbation of preexisting depression by DMPA was found (3, 4). There has been some evidence of increased depression in the postnatal period for NET-EN users (5).

    Headache is a common reason for stopping progestin injections, but severity tends to decrease over time. Most women using progestin injections do not have headaches, and preexisting tension headaches or migraines usually do not worsen.

    Although bone mineral density may decrease when estrogen levels are low due to progestin injection use, there is no evidence of increased fracture risk, and bone density scanning is not recommended (6, 7

    Mild, reversible deterioration of glucose tolerance may occur. While it is known that DMPA can alter lipoproteins, lowering high-density lipoproteins (HDL) and increasing the ratio of low-density lipoproteins (LDL) to HDL, this effect appears to be temporary and improve within 36 months of DMPA use. A similar effect would be expected with NET-EN. Unlike estrogen-based methods, progestin injections do not increase the risk of hypertension (8).

    DMPA does not appear to increase the risk of breast, ovarian, or cervical cancer.


    Progestin injections are associated with a decreased risk of

    Some evidence suggests DMPA may reduce the incidence of painful crisis in women with sickle cell disease.

    Progestin injections may be an appropriate contraceptive option for patients with a seizure disorder because it does not interact with antiseizure medications that induce liver enzymes.


    1. 1. Fotherby K, Howard G: Return of fertility in women discontinuing injectable contraceptives. J Obstet Gynaecol (Lahore) 6 Suppl 2:S110-S115, 1986. doi:10.3109/01443618609081724

    2. 2. Westhoff C, Truman C, Kalmuss D, et al: Depressive symptoms and Depo-Provera. Contraception 57(4):237-240, 1998. doi:10.1016/s0010-7824(98)00024-9

    3. 3. Singata-Madliki M, Carayon-Lefebvre d'Hellencourt F, Lawrie TA, et al: Effects of three contraceptive methods on depression and sexual function: An ancillary study of the ECHO randomized trial. Int J Gynaecol Obstet 154(2):256-262, 2021. doi:10.1002/ijgo.13594

    4. 4. Gupta N, O'Brien R, Jacobsen LJ, et al: Mood changes in adolescents using depot-medroxyprogesterone acetate for contraception: a prospective study. J Pediatr Adolesc Gynecol 14(2):71-76, 2001. doi:10.1016/s1083-3188(01)00074-2

    5. 5. Lawrie TA, Hofmeyr GJ, De Jager M, et al: A double-blind randomised placebo controlled trial of postnatal norethisterone enanthate: the effect on postnatal depression and serum hormones. Br J Obstet Gynaecol 105(10):1082-1090, 1998. doi:10.1111/j.1471-0528.1998.tb09940.x

    6. 6. Kaunitz AM, Miller PD, Rice VM, et al: Bone mineral density in women aged 25-35 years receiving depot medroxyprogesterone acetate: recovery following discontinuation. Contraception 74(2):90-99, 2006. doi:10.1016/j.contraception.2006.03.010

    7. 7. Rosenberg L, Zhang Y, Constant D, et al: Bone status after cessation of use of injectable progestin contraceptives. Contraception 76(6):425-431, 2007. doi:10.1016/j.contraception.2007.08.010

    8. 8. Berenson AB, Rahman M, Wilkinson G: Effect of injectable and oral contraceptives on serum lipids. Obstet Gynecol 114(4):786-794, 2009. doi:10.1097/AOG.0b013e3181b76bea

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