Hormone-related side effects in new users of a levonorgestrel 52-mg intrauterine device

Although the levonorgestrel 52 mg intrauterine device is locally active and has low systemic hormone exposure, hormonal intrauterine device users sometimes report hormone-related side effects.

Evaluate hormone-related adverse event rates among all participants and compare these among those who used combined hormonal or no hormonal contraception in the month before enrollment.

A total of 1714 women aged 16 to 45 years old received a levonorgestrel 52 mg intrauterine device in a multicenter phase 3 trial to evaluate contraceptive efficacy and safety for up to 10 years. This analysis evaluated a subset of participants who used combined hormonal or no hormonal contraception in the month prior to device placement. We assessed all nonexpulsion, nonbleeding-related events with ≥1% incidence at 180 days with a plan to include weight increase regardless of incidence; we excluded events considered nonhormonal. We computed 180-day side effect frequency rates based on the number of days a side effect was reported during the study period. We created a multivariable model for side effect incidence at 180 days based on age, race, ethnicity, body mass index at enrollment, parity, and contraception use in the month before enrollment. For those side effects with a P value <.2 on univariate comparison between combined hormonal and no hormonal contraception users, we secondarily evaluated 360-day event rates.

Overall, 644 participants used combined hormonal contraception (primarily oral [n=499, 77.5%]) and 855 used no hormonal method before intrauterine device placement. Individual side effect rates over the first 180 days did not differ between prior combined hormonal and no hormonal contraception users except for acne (84 [13.0%] vs 73 [8.5%], respectively), P=.006, odds ratio 1.61 (95% confidence interval 1.15-2.24). However, this association was weaker after adjustment for age, race, ethnicity, obesity status, and parity (adjusted odds ratio 1.40, 95% confidence interval 0.99-1.98) At 360 days, prior combined hormonal contraception users were more likely to report acne (101 [15.7%] vs 91 [10.6%], respectively, P=.005) and orgasm/libido problems (20 [3.1%] vs 12 [1.4%], respectively, P=.03). Over the first 180 days, all side effects other than acne were reported in less than 3% of days; acne was reported an average of 13 days (7.4%) per prior combined hormonal contraception user and 9 days (5.0%) per prior nonhormonal contraception user (P<.0001). Discontinuation for evaluated side effects occurred in 83 (5.5%) participants with no difference between those who used combined hormonal (36 [5.6%]) or no hormonal contraception (47 [5.5%], P=1.0) before study entry.

Using combined hormonal contraception prior to levonorgestrel 52 mg intrauterine device placement is weakly associated with reporting hormonally related side effects like acne. Only a small percentage of levonorgestrel 52 mg intrauterine device users experienced potentially hormone-related side effects during the initial 6 months of use that resulted in discontinuation.