A pilot study: estradiol/progesterone effect on cervico-vaginal cytokines in premenopause and postmenopause

Abstract

Objective: We compared cervico-vaginal cytokines in hormone therapy (HT)-treated postmenopausal women with premenopausal women and explored the association of serum estradiol (E2) and progesterone (P4) with cervico-vaginal cytokines.

Methods: Postmenopausal women were treated with oral E2 1 mg/day for 28 days, with oral P4 100 mg/day added for the last 14 days. Premenopausal women were evaluated over one menstrual cycle. Serum E2 and P4 levels and cervico-vaginal cytokines interleukin (IL)-8 and IL-1β were measured at baseline, 14 days, and 28 days and were estimated by specific enzyme-linked immunosorbent assays.

Results: Among nine postmenopausal and seven premenopausal women, cervico-vaginal IL-8 levels were highest at baseline, decreased on day 14, and remained stable thereafter. Cervico-vaginal IL-1β levels were highest at baseline, decreased on day 14, and remained stable with HT in postmenopausal women while they increased in premenopausal women. Postmenopausal women treated with HT and premenopausal women had similar changes in IL-8 and IL-1β. Serum E2 levels negatively correlated with IL-8 and IL-1β levels. Increased serum E2 from HT was correlated with the decreased IL-8 level from baseline to day 14 (p = 0.03).

Conclusion: Exogenous E2 and P4 decreased the cervico-vaginal IL-1β and IL-8 to those levels found in premenopausal women. These findings require confirmation in a larger prospective study.

摘要

目的：比较应用激素治疗(HT)的绝经后妇女与绝经前妇女的宫颈阴道细胞因子, 探讨血清雌二醇(E2)、孕酮(P4)与宫颈阴道细胞因子的关系。

方法：绝经后妇女口服雌二醇1 mg/d, 连服28d, 同时在后14天加用P4 100 mg/d, 口服。对绝经前妇女在一个月经周期内进行评估。分别于基线、第14天、第28天测定血清E2、P4水平及宫颈阴道细胞因子白细胞介素(IL)-8、IL-1β水平, 并用特异性酶联免疫吸附法进行评估。

结果：在9名绝经后妇女和7名绝经前妇女中, 宫颈阴道IL-8水平在基线时最高, 第14天下降, 此后保持稳定。宫颈-阴道IL-1β水平在基线时最高, 在第14天下降, 此后应用HT的绝经后妇女的宫颈-阴道IL-1β水平保持稳定, 而绝经前妇女的宫颈-阴道IL-1β水平升高。接受HT治疗的绝经后妇女和绝经前妇女IL-8和IL-1β的变化相似。血清E2水平与IL-8、IL-1β水平呈负相关。从基线到第14天, HT患者血清E2水平升高与IL-8水平下降有关(p=0.03)。

结论：外源性E2和P4使宫颈阴道IL-1β和IL-8水平降低至绝经前妇女水平。这些发现需要在一项更大的前瞻性研究中得到证实。

Keywords:

• Cervico-vaginal cytokines
• interleukin-1β
• interleukin-8
• estradiol
• progesterone

Potential conflict of interest

I. S. received an unrestricted research grant from TherapeuticsMD. B. B. is an employee of TherapeuticsMD, owns stock/stock options of the company, and is also a Board member of TherapeuticsMD. S. M. is an employee of TherapeuticsMD and owns stock/stock options of the company. D. F. A. serves as a consultant for Abbvie, Actavis, Agile Therapeutics, Bayer Healthcare, Endoceutics, Exeltis, InnovaGyn, and TherapeuticsMD; and has received research support from Actavis, Bayer Healthcare, Endoceutics, Glenmark, Merck, Myovant, ObsEva, Radius Health, Shionogi, and TherapeuticsMD. T. P., A. S., and T. J. have no conflict of interest.

Source of funding

This study is supported by an unrestricted research grant from TherapeuticsMD.