See also Hormone Replacement Therapy

I. Mechanisms of action

  1. Inhibit ovulation by suppressing LH and FSH
  2. Thicken and decrease amount of cervical mucus, inhibiting sperm penetration
  3. Make endometrium thin and atrophic, inhospitable to fertilized egg
  4. Favor premature luteolysis

II. Different forms

  1. "Minipill"
  1. Daily, with no "off" period like with combined OC's
  2. One-year failure rate perfect use 0.5% (0.1% for combined OC's!); however, one head-to-head study of Micronor vs. Norinyl 1/50 and Nordette found no sig. diff. in pregnancy rates!)
  3. Very unforgiving if you take it even a few hrs. late; emphasize need for backup method if miss a pill
  4. If miss a pill, take it as soon as remember and the next day's at normal time; if >3h late, use backup method for 48h
  5. If miss 2 pills, use backup method; restart minipills and double-up for 2d; come in for preg. test if no menses in 4-6wks
  6. Less effective in women who continue to ovulate when on them; these are the women who have reg. periods while on the minipill
  7. Use backup method for first 28d
  8. Expect menses at least Q6wks; come in for preg. test if don't get
  9. Median time from discontinuation to conception < 3mos
  10. Less extensively studies than other methods
  1. Depo-Provera (medroxyprogesterone acetate)
  1. 150mg IM Q3mos
  2. Need backup method for first 2wks, but not if shot give <5d after start of menses
  3. One-year failure rate perfect use 0.3%
  4. Median time from discontinuation to conception 6 mos
  5. Actually lasts for about 14wks
  6. Higher dose of progestin than Norplant or minipill
  1. Norplant
  1. 6 silicone capsules containing levonorgestrel (35-85 ug daily release)
  2. Removed from U.S. marked in 2002 due to litrigation re: difficulties with removal
  1. Implanon
    1. Uses etonogestrel in an implant
    2. Can remain in 3y
    3. Removed from U.S. market-replaced by Nexplanon
  1. Nexplanon
    1. Replaces Implanon-Only difference is addition of barium sulfate to make it visible on x-ray
    2. Contains a single implant of etonorgestrel, implanted subdermally 3-4" above medial epicondyle in nondominant arm
    3. Lasts 3y
    4. Can be placed any time in menstrual cycle after pregnancy is excluded, though optimally in days 1-5 of menstrual cycle (in the latter case is effective immediately after insertion; else backup method should be used for first 7d)
    5. Can be placed in first 5d post-abortion of postpartum day 21-28 (unless breastfeeding un which case should wait until after day 28; lactating women should use barrier method for first 7d)
    6. Ovulation returns 10-14d after removal
  2. Levonorgestrel intrauterine device (IUD) (Mirena)-Click link for details

III. Contraindications (absolute and relative)

  1. Pregnancy
  2. Unexplained uterine bleeding
  3. Certain meds (see below)
  4. Active thrombotic event
  5. Known or suspected breast Ca (must do exam to r/o!)
  6. Migraines
  7. Cardiac disease (warning included in labelling based on experience with OC's; unknown risk)
  8. Depression
  9. Unlike combined oral contraceptives, progestin-only contraception is not contraindicated in smokers
  10. Overweight (may have reduced effectiveness)

IV. Advantages

  1. No estrogen
  2. No known serious long-term effects
  3. Reduced dysmenorrhea and mittelschmerz
  4. Decreased risk of endometrial and ovarian Ca
  5. Decreased risk of PID?
  6. OK for breastfeeding

V. Adverse effects

  1. Menstrual irregularity and amenorrhea
  1. Most common with Depo and implantable contraceptives, less but still common with minipill
  2. Total amount of blood losss is not increased; just unpredictable
  3. With prolonged use, infrequent bleeding or amenorrhea may occur
  4. May treat with exogenous estrogens (e.g. low-dose OC's) or NSAID's if necessary
  5. On the other hand, some see amenorrhea as an advantage; may reduce anemia
  1. For Depo, 30-50% amenorrheic at end of 1st year; 70% at end of 2nd year; 80% at end of 5th year.
  2. For Nexplanon, 15% have prolonged bleeding and 16% menometrorrhagia
  1. Weight gain (about 1-2lb/yr); less for minipill than with combined OC's
  2. Breast tenderness (can tx with vit. E 400IU BID)
  3. Depression and emotional lability-FAR FROM CLEAR!
    1. A nonrandomized prospective study of 1,405 women using either Depo-Provera (12mo f/u) or Norplant (2y f/u) found that depression scores actually improved slightly in women who continued the tx through the study period (Contraception 57:237, 1998--JWWH)--note to myself: there are some obvious methodologic problems w/this study...
  4. Headaches (inc. pseudotumor cerebri-like sd.)
  5. Androgenic sx (hirsutism, acne)-rare
  6. Norplant can be difficult to remove
  7. May get ov. cysts with Norplant and minipill
  8. HDL tends to fall with Depo (not with Norplant)
  9. Decreases in bone density
  1. Likely due to suppression of ovarian estrogen production caused by decreased gonadotropin secretion
  2. May be reversible 1-2y after discontinuation
  3. FDA recommends against use in adolescents for > 2y at a time for this reason
  4. Nonrandomized trials
    1. Comparison of bone mineral density (by DEXA) in 30 women on depo x > 5y vs matched (age, race, BMI, but not smoking!) with 30 premenopausal and 30 postmenopausal non-depo users; found sig. reduced (6-8%) BMD in both lumbar spine and femoral neck in depo pts vs. premenopausal controls; postmenopausal controls had lower BMD (BMJ 303:13, 1991)
    2. Comparison of BMD (femoral neck, by plain X-ray!) in 75 women on depo x > 3y vs matched (by age and BMI) with non-depo users, all without smoking or chronic EtOH use; no sig. diff found (Asia Oceania J. Obs. Gyn. 20:269, 1994)
    3. Mini-pill (as opposed to barrier) use in a nonrandomized controlled trial in 20 breastfeeding women was associated with sig. less decrease in lumbar bone mineral density over 1y postpartum (Clin. Endocrinol. 41:739, 1994-abst)
    4. Group of adolescent girls followed with baseline and 1y lumbar bone mineral density by DEXA; 15 on Depo, 7 on Norplant, 9 on combined OC's, 17 on no hormonal tx. Baseline BMD similar in all groups; at 1y, had decreased 1.5% in Depo users and increased 2.5% in Norplant users, 1.5% in combined OCP users, and 2.9% in non-hormonal users. (J. Peds 129:671, 1996-abst)
    5. In a nonrandomized comparison of 200 Depo users (2-26y of use) with 350 controls, lumbar spine BMD was 7.2% in users (sig.); the difference was less in women who had started Depo after age 20 and those who had used < 15y (Obs. Gyn. 92:569, 1998--JW)
    6. In a study comparing 183 women 18-39yo with age-matched controls found that after adjustment for other risk factors known to affect bone density, Depo users had sig. lower mean bone density at the lumbar spine, femoral neck, and greater trochanter. There was an inverse relationship between bone density and duration of Depo use (Obs. Gyn. 93:233, 1999--AFP)
    7. In a cohort study of 17 adolescents using depo-Provera, femoral & L-spine neck BMD after 1y and 2y of use were lower than at baseline (-2.5% decline at 2y).  Differences at 1y were sig. but because some pts dropped out, not sig. @ 2y  (J. Adol. Health 32:257, 2003)
    8. In a cohort study of 174 girls 14-18yo 81 of whom were using DMPA, overall mean BMD values were sig. lower in DMPA users but site-specific BMD's (e.g. spine) were not sig. different.  (Contraception 69:99, 2004--JW)
    9. In a prospective study in 248 women starting depo-Provera and 360 women using nonhormonal contraception, at 5y, women who had continued on depo-Provera had sig. greater decreases in hip and lumbar BMD compared with non-hormonally-treated patients.  At 96wks after cessation of depo-Provera, however, BMD had returned to baseline levels (Contraception 74:90, 2006--JW)
    10. In a case-control study of 17,527 women 20-44yo with first-time fractures and 70,130 matched controls, after adjustment for potential confounders, current use of depot-medroxyprogesterone acetate was associated with sig. higher fx risk compared with never use, with a dose-response relationship (OR 1.2, 1.4, and 1.5 with history of 1-2, 3-9, and 10 or more doses, respectively). (J. Clin. Endocrinol. Metab. 8/4/2010-e-pub ahead of printing at
  5. Randomized trials
    1. 22 women avg. age 32.6y randomized to Depo vs. Norplant. Over 6mo, forearm bone density increased by 3% with Norplant and remained stable with Depo, a sig. difference (Contraception 52:35, 1995-abst)
    2. In a study in 110 women 18-33yo randomized to medroxyprogesterone acetate 150mg IM Q3mos vs. combined OCPs, after 2y, MPA goup had 5.7% drop in spinal BMD (sig.); the OCP group had no sig. change(Obs. Gyn. 103:899, 2004--AFP)
  6. Use of estrogen to prevent bone loss in pts on progestin-only contraception
    1. In a study of 39 women (mean age 37yo) on IM medroxyprogesterone acetate x > 2y with below-average lumbar spine BMD randomized to conjugated equine estrogens 0.625mg PO QD vs. placebo (all receiving continued MPA) x 2y, the estrogen recipients had 1% increase in average L-spine BMD bt dexa, vs. 2.6% drop in placebo group (sig.) (J. Clin. Endo.Metab. 88:178, 2003--abst)
    2. In a study of 123 adolescents on DMPA Q12wks for contraception randomized to monthly injections of estradiol cypionate vs. placebo, at 24mos, % change BMD was sig. less bad in estradiol group in the spine (+2.8% vs. -1.8%) and femoral neck (+4.7% vs. -5.1%) (Am. J. Obs. Gyn. 192:42, 2005--abst)
  1. Breast Cancer--Click link for details
  1. Diabetes Mellitus
    1. In a prospective study of 904 hispanic women with h/o gestational DM but then with normal postpartum OGTT's, about half of whom used OC's (those who were breastfeeding used progestin-only OC's; none used non-oral hormonal contraception) followed for maximum 7.5y with yearly OGTT, annual incidence of type 2 DM was 8.7% for non-OC users, 10.7% for combined-OC users (no sig. diff. from non-OC users), and 26.5% for progestin-only OC users (sig. diff. from other two groups). The increased incidence of DM in progestin only users persisted after adjustment for insulin tx during index pregnancy, weight change while on OCP's, completion of an additional pregnancy, or prior use of hormonal contraception. The excess risk in progestin-only OC users increased with duration of use. There was NO difference in risk of DM between breastfeeding and non-breastfeeding women who were not using any hormonal contraception (JAMA 280:533, 1998)
  2. May be associated with higher risk of cervicitis (per one prospective study, compared with oral contraceptives or non-hormonal contraception--Sex. Transm. Dis. 31:561, 2004--JW)

VI. Drug interactions

  1. Cytadren can reduce effectiveness
  2. All anticoagulants except valproate can seriously reduce effectiveness
  3. So can rifampin
(Sources include Core Content Review of Family Medicine, 2012)