Counseling before treatment improves adherence. Counseling about menstrual changes, especially the absence of menses associated with DMPA-IM and L-IUS, can significantly increase user satisfaction and continuation rates.23,24 In a prospective study of new users of DMPA-IM, women who were told about the possibility of amenorrhea were 2.5 times more likely to continue use at 1 year than those who were not given this information.23 In fact, surveys of women’s preferences indicate that most women prefer the convenience, comfort, and freedom of less frequent or absent menses.25 Because the decision whether or not to menstruate is a personal one, this is an important issue to discuss with a patient selecting a contraceptive method.
Weight gain
Concern about weight gain can be significant enough for some women to pose a barrier to hormonal contraceptive selection and compliance. Variable effects of DMPA-IM on body weight have been reported, ranging from nonsignificant changes26,27 to gains of approximately 3 kg to 4 kg at 1 year.28,29 However, the most pronounced weight changes occurred in women who were overweight at the initiation of use or who may have been inherently predisposed to gain weight.28,29
In a long-term study of Thai women using either DMPA-IM or a nonhormonal intrauterine device, weight gain in both groups was comparable after 10 years of use (10.9 and 11.2 kg, respectively).30 Furthermore, in the only randomized, placebo-controlled trial to assess weight gain, normal-weight women observed during the first 2 menstrual cycles following the initial injection of DMPA-IM did not experience weight gain.31
Data from 1-year multicenter clinical trials with the NE-patch, EE-ring, and L-IUS indicate that users of these methods experience minimal (<1 kg) or no weight gain. ,32,33 However, long-term follow-up of women using L-IUS for 12 years found an increase in body weight of 0.49 kg/year during the study period and a mean overall increase of 5.7 kg.34
Mood changes
Although mood changes are often cited by women as a reason for discontinuing hormonal contraception,2 data from clinical trials indicate that DMPA-IM does not cause mood changes or worsen existing depressive symptoms. Fewer than 2% of 3857 US women who used DMPA-IM in a 1-year multicenter trial reported depression.19 Other studies specifically assessing mood changes in an adolescent health clinic35 and inner-city family planning clinics36 failed to find any adverse impact of DMPA-IM on mood. Only 1 study of women enrolled in a health maintenance organization found an association between DMPA-IM and symptoms of depression, but a causal relationship could not be established.37
To date, no studies have specifically examined the effects of the other nondaily hormonal contraceptive options on mood. L-IUS product labeling states that depression has been reported in more than 5% of patients,5 while 1-year clinical trials report emotional lability in 1.5% of NE-patch users and 2.8% of EE-ring users.32,38 However, in a small comparative trial, there were no reports of depression among 121 EE-ring users, whereas it was reported by 4.8% of 126 women using a combined oral contraceptive containing 30 μg ethinyl estradiol and 150 μg levonorgestrel.21
Delivery system–related side effects
All nondaily options have specific side effects related to local effects or the delivery system. DMPA-IM may cause pain on injection, but this is reported as an adverse event by fewer than 1% of subjects.13
In a US clinical trial of the NE-patch, application-site reactions were reported by 20% of participants, leading to discontinuation by 2.6% of women in the patch group; 4.6% of patches were replaced for either complete (1.8%) or partial detachment (2.8%).22
In a 1-year multicenter study of the EE-ring in 2322 women, common complaints were vaginitis (5.6%), leukorrhea (4.8%), and device-related events (4.4%) consisting of foreign body sensation, coital problems, and expulsion. The latter problem can occur during removal of a tampon or during bowel or bladder emptying, necessitating immediate reinsertion of the ring or replacement with a new ring.7,32
Expulsion is also a problem with L-IUS and can result in unintended pregnancy. During the first 2 years following insertion, L-IUS was discontinued by 6.6% of 256 women as the result of expulsion, which occurred significantly more frequently among women with heavy menstrual bleeding than those with normal bleeding (13% vs 5%, P=.01).20 Other potential device-related effects of L-IUS include pelvic inflammatory disease, embedment or perforation, and sepsis.5
Long-term safety profiles
Cancer risks
To date, cancer risks associated with long-term use have been investigated only for DMPA-IM and combined oral contraceptives in large epidemiological studies ( Table 2 ). Because women’s concerns regarding the risk of breast cancer may make them reluctant to use a hormonal method of contraception, it is particularly important for clinicians to emphasize the evidence showing that use of hormonal contraceptives is not associated with an increase in the overall risk of breast cancer. Though a large-scale reanalysis of 54 studies found a slight increase in breast cancer risk among current combined oral contraceptive users (relative risk [RR]=1.24; 95% confidence interval [CI], 1.15–1.33), this risk decreased over time and was the same as that of combined oral contraceptive never-users 10 or more years after cessation of use (RR=1.01; 95% CI, 0.96–1.05).39 Similarly, a pooled analysis of DMPA-IM data from the World Health Organization (WHO) and New Zealand trials, which were completed in the early 1990s, also found a slight increase in breast cancer risk among current users (RR=1.50; 95% CI, 1.0–2.2), but showed no increase in the overall risk of breast cancer among ever-users.40