Transdermal estradiol prevents premenstrually-recurrent genital herpes in perimenopausal women

      Introduction: Some women suffer cyclical recurrences of genital herpes (c-RGH) immediately prior to menstruation (herpes catamenialis), and we have previously shown that these episodes can be effectively prevented using aciclovir in the luteal phase only. c-RGH is more likely to occur in perimenopausal women whose immunity is diminished by premenstrual dysphoric disorder (PMDD), which itself can be successfully treated with transdermal estradiol, with or without a Levonorgestrel-Intrauterine System (LNG-IUS).
      Aim: To observe the frequency of herpes recurrences in women commencing transdermal estradiol treatment for perimenopausal PMDD.
      Methods: 12 perimenopausal women median age 41 years (range 36–45) presented between 2006 and 2015, each meeting the criteria for PMDD subsequently defined in DSM-5. Each had at least 4 consecutive monthly episodes of c-RGH (culture-proven HSV2) before some took luteal-phase aciclovir, then all switched to transdermal 17-beta estradiol gel 0.5 mg (Sandrena, Organon) daily for 14 days in the luteal phase or continuously for those using LNG-IUS. Subjects self-reported mood with a modified daily symptom chart and herpetic symptoms over 9 months follow-up during which no aciclovir was taken pre-emptively. Intention-to-treat (ITT) analysis included 10 cycles where treatment was omitted in error and both conditions recurred.
      Results: All women experienced substantial or complete relief of PMDD in all but three treated cycles. Only 13 symptomatic c-RGH episodes occurred when treatment was taken correctly in 108 woman-months’ observation. PMDD … Herpes Total episodes observed in 9 months (ITT, Expected 108) … 13 … 23 Mean episodes per month Observed/Expected (one per month). 0.12 … 0.21 Probability was calculated using a Student's t-test … p < 0.001 … p < 0.01.
      Discussion: This work confirms that transdermal estradiol is an effective treatment for perimenopausal PMDD. It stabilises the hormonal milieu throughout the cycle and thereby diminishes luteal phase immune suppression which is known to exacerbate a wide range of systemic and dermatological conditions. This explains why it can be used as a novel and biologically plausible method of preventing premenstrually-recurrent genital herpes (herpes catamenialis) without recourse to antiviral therapy.