Clomiphene citrate affects cervical mucus and endometrial morphology independently of the changes in plasma hormonal levels induced by multiple follicular recruitment
Massai MR,Lesobre V,Bergeron C,Frydman R,Bouchard P,de Ziegler D
Published June 1993Fertility and Sterility, 59(6), 1179-1186
Massai, M. R., Lesobre, V., Bergeron, C., Frydman, R., Bouchard, P., & de Ziegler, D. (1993). Clomiphene citrate affects cervical mucus and endometrial morphology independently of the changes in plasma hormonal levels induced by multiple follicular recruitment. Fertility and Sterility, 59(6), 1179-1186. https://doi.org/10.1016/s0015-0282(16)55973-1
Massai MR, Lesobre V, Bergeron C, Frydman R, Bouchard P, de Ziegler D. Clomiphene citrate affects cervical mucus and endometrial morphology independently of the changes in plasma hormonal levels induced by multiple follicular recruitment. Fertil Steril. 1993;59(6):1179-1186. doi:10.1016/s0015-0282(16)55973-1
Massai, M. R., et al. "Clomiphene citrate affects cervical mucus and endometrial morphology independently of the changes in plasma hormonal levels induced by multiple follicular recruitment." Fertility and Sterility, vol. 59, no. 6, 1993, pp. 1179-1186.
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4 institutions
Service d'Endocrinologie et des Maladies de la Reproduction, Hôpital de Bicêtre, France.
Université de Versailles Saint-Quentin-en-Yvelines03mkjjy25
On set hormone levels, clomiphene lowered mucus and delayed lining
Clomiphene citrate lowered cervical mucus scores and delayed the uterine lining's late maturation in a small experiment. French researchers held estrogen and progesterone at set levels in 24 women. Some also took clomiphene. Early lining changes looked similar in both groups.
Study at a glance: Clomiphene lowered cervical mucus scores and delayed lining maturation. Source: Massai MR et al., 1993, PMID 8495762.
Key Findings
The study enrolled 24 women aged 31 to 39: 18 with regular ovulatory cycles and drug-suppressed ovaries, and 6 with premature ovarian failure.
Cervical mucus scored 5.5 in women who took clomiphene citrate and 13.6 in controls, on a 0 to 15 scale (P < 0.01).
On day 20, biopsies of the uterine lining looked similar in the clomiphene and control groups. On day 24, the clomiphene group showed delayed secretory development.
On day 24, progesterone receptor staining persisted only in the lining's stroma, with no difference between the clomiphene and control groups.
Interpretation
This experiment compared clomiphene citrate to a control in 24 women. Doctors at French university hospitals gave everyone the same estrogen and progesterone, at normal levels, the whole time. The matched hormone levels isolate clomiphene's own effect from the high estrogen of a stimulated cycle. The day 20 comparison group drew on 6 women with premature ovarian failure, reported in an earlier paper. The authors note that high estrogen in treatment cycles may partly offset clomiphene's effect on the lining. The findings support larger studies of clomiphene's effects on mucus and the uterine lining.
RRM Context
Charting-based methods such as the Creighton Model record cervical mucus as a sign of fertility. A restorative approach asks first why ovulation fails. In this experiment, a drug given to induce ovulation lowered mucus scores in women whose hormones were held at set levels.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To analyze the effects of clomiphene citrate (CC) on cervical mucus (CM) and endometrial morphology independently of hormonal changes encountered when CC is administered for ovulation induction.
Design
Volunteers whose ovarian functions were temporarily suppressed (n = 18) by a long-acting GnRH agonist and 6 women of similar age suffering from premature ovarian failure (POF) received E2 and P. Half of the women also received CC (50 mg/d, days 2 to 6).
Setting
Tertiary University Institution, Hôpital A. Béclère.
PATIENTS,
Participants
Eighteen volunteers suffering from infertility not related to a uterine cause and 6 women of similar age suffering from POF.
Main Outcome Measures
Plasma gonadotropins, E2, and P were measured at baseline to confirm that the ovaries were inactive and twice weekly during physiological E2 and P replacement. Cervical mucus was analyzed on day 14 and scored from 0 to 15. Endometrial biopsies were obtained on replacement days 20 and 24 for conventional histology and immunocytochemistry analysis of estrogen receptors and progesterone receptors (PR). Premature ovarian failure women whose results have been previously published served as controls for day 20 biopsies.
Results
Cervical mucus scored lower in women who received CC (5.5 +/- 3.2) than in controls (13.6 +/- 4.7, mean +/- SEM). On day 20, endometrial findings were similar in women treated with CC and in controls. On day 24, specimens showed a significant delay in endometrial maturation in women treated with CC. On day 24, only staining for PR selectively persisted in endometrial stroma, and no difference was observed between women who received CC and controls.
Conclusion
Our results indicate that CC significantly alters CM quality and late luteal phase endometrial morphology despite physiological levels of plasma E2 and P. Hence, clinicians should monitor E2 levels when using CC, and caution should be exerted when supraphysiological levels of E2 are not present to counterbalance the effects of CC on the CM and the endometrium.
