The most important medical reason women discontinue use of DMPA and other progestinonly methods is persistent irregular vaginal bleeding. A variety of medications are used to stop this bleeding. Many are effective in terminating individual bleeding episodes, but a systematic review concluded that none improved continuation rates long term (222). New approaches include mifepristone and low-dose doxycycline. Mifepristone is of interest because irregular bleeding with DMPA was related to the down-regulation of endometrial estrogen receptors. Treatment with 50 mg of mifepristone every 2 weeks increases endometrial estrogen receptors and reduces breakthrough bleeding in new users of both DMPA and the levonorgestrel progestin implant (223). Another line of investigation concerns endometrial matrix metalloproteinase, which appears to play a regulatory role in the breakdown of the endometrium to produce normal menstruation. Treatment with doxycycline inhibits matrix metalloproteinase production in the endometrium in women after insertion of levonorgestrel subdermal implants (224). Five-day courses of either mifepristone 25 mg twice a day for one day, followed by EE 20 μg per day for 4 days, or doxycycline 20 mg twice a day for 5 days, reduced bleeding days by about 50% when compared to placebos during a 6-month randomized trial in women treated for prolonged or frequent bleeding occurring with etonogestrel subdermal implants (225). Capsules of 20 mg doxycycline are sold in the United States for treatment of periodontal disease.
DMPA use is commonly associated with weight gain, and that is one of the principal reasons women discontinue use. A large study is representative of the literature. Three cohorts of women who chose their method of contraception were followed for 36 months with measurements of weight and body fat. DMPA users gained an average of 5.1 kg. The cohort using OCs over the same interval gained only 1.47 kg, slightly less than the 2.05 kg gained by the cohort not using any hormonal contraception. Total body fat increased 4.14 kg in the DMPA cohort, while the increase in the OC users was 1.9 kg, only slightly more than the 1.17 kg in the nonhormonal contraceptive cohort. Many women were followed for 2 years after discontinuing DMPA. Those who chose nonhormonal methods after discontinuing DMPA lost a mean of 0.42 kg each 6 months. Those who chose to use oral contraceptives gained a mean of 0.43 kg each 6 months during the follow-up interval (226).
Weight gain during the first 6 months and self-reporting of increased appetite are strongly predictive of continued weight gain. Women who gained less than or equal to 5% of body weight in the first 6 months gained a mean of 2.49 kg by 36 months, while those who gained more than 5% by 6 months gained a total mean of 11.08 kg by 36 months (227). Studies are needed of interventions to prevent the weight gain. At minimum, women considering DMPA need to know the possibility of significant weight gain and be advised to avoid calorie-dense foods and weigh themselves regularly. Ideally they should be weighed when they return for subsequent injections so they can be counseled about the need for avoiding further gain. Women who gain 5% of body weight by 6 months should consider other contraceptive options.
DMPA persists in the body for several months in women who used it for long-term contraception, and return to fertility may be delayed. It is reassuring that 70% of former users desiring pregnancy conceive within 12 months, and 90% conceive within 24 months after terminating DMPA use (228).