Abstract：
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: A total of 1714 women aged 16-45 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 non-expulsion, non-bleeding-related events with ≥1% incidence at 180 days with a plan to include weight increase regardless of incidence; we excluded events considered non-hormonal. 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 <0.2 on univariate comparison between combined-hormonal and no-hormonal contraception users, we secondarily evaluated 360-day event rates.
RESULTS: Overall, 644 participants used combined hormonal contraception (primarily oral [n=499, 77.5%]) and 855 used no hormonal method before IUD 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%] versus 73 [8.5%], respectively), p=0.006, OR 1.61 (95% CI 1.15-2.24). However, this association was weaker after adjustment for age, race, ethnicity, obesity status, and parity (aOR 1.40, 95% CI 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=0.005) and orgasm/libido problems (20 [3.1%] vs. 12 [1.4%], respectively, p=0.03). 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 non-hormonal contraception user (p<0.0001). 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.
CONCLUSIONS: Using combined hormonal contraception prior to levonorgestrel 52 mg intrauterine device placement is only 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.
OBJECTIVE: 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.
METHODS: A total of 1714 women aged 16-45 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 non-expulsion, non-bleeding-related events with ≥1% incidence at 180 days with a plan to include weight increase regardless of incidence; we excluded events considered non-hormonal. 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 <0.2 on univariate comparison between combined-hormonal and no-hormonal contraception users, we secondarily evaluated 360-day event rates.
RESULTS: Overall, 644 participants used combined hormonal contraception (primarily oral [n=499, 77.5%]) and 855 used no hormonal method before IUD 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%] versus 73 [8.5%], respectively), p=0.006, OR 1.61 (95% CI 1.15-2.24). However, this association was weaker after adjustment for age, race, ethnicity, obesity status, and parity (aOR 1.40, 95% CI 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=0.005) and orgasm/libido problems (20 [3.1%] vs. 12 [1.4%], respectively, p=0.03). 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 non-hormonal contraception user (p<0.0001). 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.
CONCLUSIONS: Using combined hormonal contraception prior to levonorgestrel 52 mg intrauterine device placement is only 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.
摘要：
背景：尽管左炔诺孕酮52mg宫内节育器是局部活跃的，并且全身激素暴露较低，激素宫内节育器使用者有时会报告激素相关的副作用。
目的：评估所有参与者的激素相关不良事件发生率，并比较在入组前一个月使用联合激素或无激素避孕的参与者之间的不良事件发生率。
方法：在一项多中心3期试验中，共有1714名年龄在16-45岁的女性接受了52mg左炔诺孕酮宫内节育器，以评估长达10年的避孕效果和安全性。该分析评估了在设备放置前一个月使用联合激素或不使用激素避孕的参与者的子集。我们评估了所有不驱逐的情况，180日时发生率≥1%的非出血相关事件,并计划包括体重增加,无论其发生率如何;我们排除了非激素性事件.我们根据研究期间报告副作用的天数计算了180天的副作用频率。我们创建了一个基于年龄的180天副作用发生率的多变量模型，种族,种族,入学时的体重指数，奇偶校验，以及在入学前一个月使用避孕药具。对于联合激素和非激素避孕使用者之间的单变量比较，p值<0.2的副作用，我们再次评估了360天事件发生率。
结果：总体而言，644名参与者使用联合激素避孕（主要是口服[n=499，77.5％]），855名参与者在放置IUD之前没有使用激素方法。前180天的个体副作用率在先前的联合激素和无激素避孕使用者之间没有差异，除了痤疮（84[13.0％]对73[8.5％]，分别)，p=0.006，OR1.61（95%CI1.15-2.24）。然而,在调整了年龄后，这种联系减弱了，种族,种族,肥胖状态，和平价(aOR1.40，95%CI0.99-1.98)在360天，先前的联合激素避孕药使用者更有可能报告痤疮（101[15.7％]与91[10.6%]，分别,p=0.005）和性高潮/性欲问题（20[3.1%]与12[1.4%]，分别,p=0.03)。在最初的180天里，除痤疮以外的所有副作用均在少于3%的天数内报告;痤疮的平均发生率为13天(7.4%),平均发生率为9天(5.0%)(p<0.0001).83名（5.5％）参与者停止评估的副作用，使用联合激素（36[5.6％]）或不使用激素避孕（47[5.5％]）的参与者之间没有差异，p=1.0）进入研究前。
结论：在放置左炔诺孕酮52mg宫内节育器之前使用联合激素避孕仅与报告激素相关的副作用（如痤疮）弱相关。只有一小部分左炔诺孕酮52mg宫内节育器使用者在使用的最初6个月内经历了潜在的激素相关副作用，导致停药。
目的：评估所有参与者的激素相关不良事件发生率，并比较在入组前一个月使用联合激素或无激素避孕的参与者之间的不良事件发生率。
方法：在一项多中心3期试验中，共有1714名年龄在16-45岁的女性接受了52mg左炔诺孕酮宫内节育器，以评估长达10年的避孕效果和安全性。该分析评估了在设备放置前一个月使用联合激素或不使用激素避孕的参与者的子集。我们评估了所有不驱逐的情况，180日时发生率≥1%的非出血相关事件,并计划包括体重增加,无论其发生率如何;我们排除了非激素性事件.我们根据研究期间报告副作用的天数计算了180天的副作用频率。我们创建了一个基于年龄的180天副作用发生率的多变量模型，种族,种族,入学时的体重指数，奇偶校验，以及在入学前一个月使用避孕药具。对于联合激素和非激素避孕使用者之间的单变量比较，p值<0.2的副作用，我们再次评估了360天事件发生率。
结果：总体而言，644名参与者使用联合激素避孕（主要是口服[n=499，77.5％]），855名参与者在放置IUD之前没有使用激素方法。前180天的个体副作用率在先前的联合激素和无激素避孕使用者之间没有差异，除了痤疮（84[13.0％]对73[8.5％]，分别)，p=0.006，OR1.61（95%CI1.15-2.24）。然而,在调整了年龄后，这种联系减弱了，种族,种族,肥胖状态，和平价(aOR1.40，95%CI0.99-1.98)在360天，先前的联合激素避孕药使用者更有可能报告痤疮（101[15.7％]与91[10.6%]，分别,p=0.005）和性高潮/性欲问题（20[3.1%]与12[1.4%]，分别,p=0.03)。在最初的180天里，除痤疮以外的所有副作用均在少于3%的天数内报告;痤疮的平均发生率为13天(7.4%),平均发生率为9天(5.0%)(p<0.0001).83名（5.5％）参与者停止评估的副作用，使用联合激素（36[5.6％]）或不使用激素避孕（47[5.5％]）的参与者之间没有差异，p=1.0）进入研究前。
结论：在放置左炔诺孕酮52mg宫内节育器之前使用联合激素避孕仅与报告激素相关的副作用（如痤疮）弱相关。只有一小部分左炔诺孕酮52mg宫内节育器使用者在使用的最初6个月内经历了潜在的激素相关副作用，导致停药。
