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Luteal Progesterone Relates to Histological Endometrial Maturation in Fertile Women

Department of Obstetrics, Gynecology, and Women’s Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07103-2757

Address all correspondence and requests for reprints to: Dr. Nanette Santoro, Department of Obstetrics, Gynecology, and Women’s Health, Division of Reproductive Endocrinology, Albert Einstein College of Medicine, Mazer 316, 1300 Morris Park Avenue, Bronx, New York 10461.

To examine the relationship between endometrial histological maturation and reproductive hormones, we studied 11 fertile women, aged 18–37 yr. All participants had had at least 1 previous pregnancy and cycled regularly, every 25–35 days. Women collected daily, first morning voided urine for measurement of estradiol and progesterone metabolite excretion, estrone conjugates (E1c), and pregnanediol glucuronide (Pdg), respectively, throughout the cycle of study. Hormones were normalized for creatinine. Between 7–9 days after home detection of a LH surge (Sure Step), participants underwent an endometrial biopsy using a small bore (Pipelle) catheter. Tissue was prepared for histological and biochemical analyses. The histological analysis is reported herein. Endometrium was dated by 3 authors (N.S., D.H., and S.P.), all of whom were blinded to the participant’s identity or timing of biopsy within her cycle. Final dating was agreed upon based upon the method of Noyes et al. E1c and Pdg were integrated throughout the cycle using the trapezoidal rule, and correlations were sought between deviation from expected histology (based upon urinary hormones and LH surge) and integrated hormone values.

E1c varied over a 2-fold range in these normal women, from 1196–2040 ng/cycle. Pdg excretion was much more variable, ranging from 22–119 µg/cycle. No relationship could be found between histological lagging of endometrial maturation and lower excretion of E1c. A moderate correlation was observed (Spearman’s r = 0.6; P < 0.05) between degree of histological maturation and integrated Pdg. Of two women with evidence of a disparity between gland and stromal development (glands lagging behind stroma by >2 days), one excreted 24 µg Pdg/cycle, the next to lowest value.

We conclude that normal fertile women experience a wide range of hormone concentrations in the face of normal endometrial maturation. Progesterone appears to exert a dose-related effect on endometrial maturation, and the techniques we used, although relatively crude clinical measures, appeared to be sufficient to detect this relationship.

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