Comparing cervical mucus changes in response to an oral progestin or oestrogen withdrawal in ovarian-suppressed women: a clinical pilot

Abstract

Purpose: Prior studies evaluating the effect of administered progestogens on peak cervical mucus have not controlled for the influence of endogenous hormones. To address this, we treated women with a gonadotropin-releasing hormone (GnRH) agonist to suppress the hypothalamus–pituitary–ovarian (HPO) axis and used transdermal oestradiol replacement to stimulate peak cervical mucus and then evaluated the effects of an oral progestin or oestradiol withdrawal.

Materials and methods: We used a crossover design to examine cervical mucus changes in women receiving transdermal oestradiol replacement following intramuscular administration of leuprolide acetate. After increasing oestradiol patches to mid-cycle levels, subjects were assigned to either 0.35 mg oral norethindrone with continuation of the patches (NET) or oestradiol withdrawal by patch removal (E2WD). We collected serum and cervical mucus samples at 0, 2, 4, 6, 22 and 24 h following the intervention.

Results: We analysed 12 cycles (6 NET, 6 E2WD) from three subjects. Baseline cervical mucus scores were favourable to sperm penetration [NET median 11, interquartile range (9–12), E2WD 13 (12–13)]. Two hours after removal of oestradiol patch or administration of norethindrone, cervical mucus scores declined [NET 8.5 (4–9), E2WD 10.5 (10–12)]. Low cervical mucus scores persisted at 24 h with NET [8.0 (7–8)] but not E2WD [10.5 (8–11)].

Conclusions: We observed a rapid decline in cervical mucus Insler scores following administration of a single dose of oral norethindrone, and scores remained lower and unfavourable through 24 h. Oestradiol withdrawal did not result in similar unfavourable changes.

摘要

目的：先前的研究评估了服用孕激素对宫颈粘液峰值的影响, 并未控制内源性激素的影响。为了解决这个问题, 我们应用促性腺激素释放激素（GnRH）激动剂以抑制女性下丘脑-垂体-卵巢（HPO）轴, 并使用经皮雌二醇替代物来刺激宫颈粘液峰, 然后评估口服孕激素或雌二醇撤退对其的影响。

材料与方法：我们采用交叉设计来检验肌内注射醋酸亮丙瑞林后接受经皮雌二醇替代的女性的宫颈粘液变化。在将雌二醇贴剂增加至中期水平后, 将受试者分配至0.35mg口服炔诺酮并继续应用贴剂（NET）或停止应用贴剂以撤退雌二醇（E2WD）。我们在干预后0、2、4、6、22和24小时收集血清和宫颈粘液样本。

结果：我们分析了来自3个受试者的12个周期（6个NET, 6个E2WD）。基线宫颈粘液评分有利于精子穿透【NET中位数11, 四分位数间距（9-12）, E2WD 13（12-13）】。停止应用雌二醇贴剂或给予炔诺酮后2小时, 宫颈粘液评分下降【NET 8.5（4-9）, E2WD 10.5（10-12）】。NET 【8.0（7-8）】, 低宫颈粘液评分持续24小时, 但E2WD不是这样【10.5（8-11）】。

结论：我们观察到服用单片口服炔诺酮后宫颈粘液Insler评分迅速下降, 并且评分在24小时内仍然较低且不利, 撤退雌二醇未导致类似的不利变化。

Keywords:

• Cervical mucus
• contraception
• Insler score
• norethindrone
• mini-pill
• progestin

Acknowledgements

The authors would like to acknowledge the OHSU Women’s Health Research Unit and especially Marci Messerle Forbes FNP and Andrea O’Donnell FNP for aiding in study coordination and sample collection.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This project is supported by The Society of Family Planning [Grant No. SFPRF15-13]. The Endocrine Technologies Support Core (ETSC) at the Oregon National Primate Research Center (ONPRC) is supported by NIH Grant P51 OD011092 awarded to ONPRC.