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The Effect of Hormonal Contraception and Menstrual Cycle Timing on Genital Herpes Simplex Virus-2 Shedding and Lesions

Micks, Elizabeth MD, MPH*; Son, Hyunju MS; Magaret, Amalia PhD†‡; Selke, Stacy MA; Johnston, Christine MD, MPH§; Wald, Anna MD, MPH‡§¶

Sexually Transmitted Diseases: January 2019 - Volume 46 - Issue 1 - p 58–62
doi: 10.1097/OLQ.0000000000000907
Original Studies

Background The effect of female sex hormones on herpes simplex virus (HSV)-2 shedding and lesion frequency is poorly understood. Previous studies suggest that hormonal contraception may increase the frequency of HSV-2 shedding.

Methods We studied HSV-2 seropositive women who performed daily genital swabbing for HSV DNA and completed diaries for genital lesions and menses. We used Poisson mixed effects models to determine if HSV detection varied throughout the menstrual cycle, or in response to hormonal contraception. We used the Wilcoxon signed-rank test and rank-sum test to determine if lesion frequency differed by cycle phase or hormonal contraceptive use.

Results In 189 women aged 19 to 46 years who collected swabs on 10,715 days and were not using hormonal contraception, HSV-2 DNA was detected on 20.9% of days in the follicular phase and 17.8% of days in the luteal phase (rate ratio, 1.19; 95% confidence interval, 1.03–1.37, P = 0.02). Genital lesions did not differ in the follicular versus luteal phase (12.8% vs. 10.7%, P = 0.07). In analyses of hormonal contraception, including 244 women, HSV-2 DNA was detected on 19.0% of days for women not using hormonal contraception and 18.3% of days for those using hormonal contraception (P = 0.50). Lesions were present on 11.1% of days for women not using hormonal contraception, and 8.7% of days for those using hormonal contraception (P = 0.66).

Conclusions In women with genital HSV-2 infection who are not using hormonal contraception, the follicular phase of the cycle may be associated with a higher frequency of HSV-2 shedding compared to the luteal phase. Lesion frequency is similar during the 2 menstrual phases. Hormonal contraception use was not observed to affect genital HSV-2 DNA detection or lesions.

Among herpes simplex virus (HSV)-2 seropositive women, the follicular phase of the cycle was associated with a higher frequency of genital HSV-2 shedding. Hormonal contraception did not affect HSV-2 shedding or lesions.

From the *Department of Obstetrics and Gynecology

Department of Biostatistics,

Department of Laboratory Medicine,

§Department of Medicine, and

Department of Epidemiology, University of Washington, Seattle, WA

Conflicts of Interest: None declared.

Sources of Funding: National Institute of Child Health and Human Development (NICHD, grant K12HD001246), National Institute of Allergy and Infectious Diseases (NIAID, grant P01 AI030731).

Correspondence: Elizabeth Micks, MD, MPH, Department of Obstetrics and Gynecology, University of Washington, 1959 NE Pacific St. Box 356460, Seattle, WA 98195. E-mail:

Received for publication May 7, 2018, and accepted August 20, 2018.

© Copyright 2019 American Sexually Transmitted Diseases Association