Progesterone is essential for endometrial receptivity and successful establishment of pregnancy. Either an insufficient progesterone concentration or an insufficient response to progesterone, therefore can lead to infertility and pregnancy loss. Assessment of the role that either progesterone insufficiency or inadequate progesterone response plays in human reproductive failure has been difficult to assess because serum progesterone concentrations fluctuate markedly, limiting the ability to characterize sufficiency of progesterone, and there are no highly reliable markers of endometrial function available. Recent evidence demonstrates exquisite sensitivity of normal endometrium to very low levels of progesterone stimulation, suggesting that progesterone insufficiency should not be a common cause of reproductive failure. Further evidence suggests that women with endometriosis, and possibly polycystic ovarian syndrome, have an altered progesterone response, which may explain some of the clinical features of these disorders and supports the hypothesis that progesterone resistance underlies some cases of human reproductive failure.
PMID 20104424 20104424 DOI 10.1055/s-0029-1242988 10.1055/s-0029-1242988 Young et al. 2010, Young 2010
Cite this article
Young, S. L., & Lessey, B. A. (2010). Progesterone function in human endometrium: clinical perspectives. Seminars in reproductive medicine, 28(1), 5-16. https://doi.org/10.1055/s-0029-1242988
Young SL, Lessey BA. Progesterone function in human endometrium: clinical perspectives. Semin Reprod Med. 2010;28(1):5-16. doi:10.1055/s-0029-1242988
Young, S. L., and B. A. Lessey. "Progesterone function in human endometrium: clinical perspectives." Seminars in reproductive medicine, vol. 28, no. 1, 2010, pp. 5-16.
Keywords
Integrins, Intercellular Signaling Peptides and Proteins, Receptors, Progesterone, Selectins, Progesterone
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Aghajanova L et al., 2010·Seminars in reproductive medicine
Progesterone plays an important role in regulating multiple events in the uterus. It controls endometrial proliferation and differentiation, which are important for uterine function. Dysregulation of progesterone signaling leads to impaired physiological functions. Indeed, aberrant expression of progesterone-regulated genes in the endometrium has been implicated in several gynecologic disorders, including endometriosis, polycystic ovarian syndrome (PCOS), and endometrial hyperplasia. Although several investigators have analyzed eutopic endometrial expression of progesterone-target genes, the genesis and consequences of progesterone resistance remain unclear. We review evidence for progesterone resistance in endometrium of women with endometriosis, PCOS, and endometrial hyperplasia, and we identify possible mechanisms associated with reduced progesterone activity in endometrium of (some) women with these gynecologic disorders that have a significant impact on women's health and well-being.
Practice Committee of the American Society for Reproductive Medicine and Practice Committee of the Society for Reproductive Endocrinology and Infertility, 2026·Fertility and sterility
Luteal phase deficiency (LPD) is a clinical diagnosis associated with abnormal luteal phase length of ≤10 days. Potential etiologies of LPD include inadequate progesterone duration, inadequate progesterone levels, or endometrial progesterone resistance. Luteal phase deficiency has been described in association with medical conditions, but also in fertile, normally menstruating women. Although progesterone is important for the process of implantation and early embryonic development, LPD has not been proven to be an independent entity causing infertility or recurrent pregnancy loss. Controversy exists regarding the multiple proposed measures for diagnosing LPD, and assuming it can be diagnosed accurately, whether treatment improves outcomes. This document replaces the document of the same name, last published in 2021 (Fertil Steril 2021;115(6):1416-23).
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, typically characterized by irregular menstrual cycles. Our study found that postpartum menstrual cycles were largely restored in PCOS patients following assisted reproductive technology (ART) therapy. However, this recovery in menstrual cycles was not associated with any specific ART procedures. Using a PCOS mouse model, we demonstrated that elevated progesterone levels during pregnancy were responsible for normalizing estrous cyclicity. Elevated levels of progesterone induce granulosa cell apoptosis and deplete large follicles, which potentially contribute to ovarian function suppression during pregnancy. Mechanistic studies indicated that progesterone decreased follicle-stimulating hormone receptor (FSHR) expression in a GATA binding protein 2 (GATA2)-dependent manner. Interestingly, the capacity of granulosa cells to convert androgens to estrogens significantly increased after progesterone withdrawal, as evidenced by elevated cytochrome P450 family 19 subfamily A member 1 (Cyp19a1) expression in granulosa cells when stimulated with FSH. Additionally, we found that progesterone administration reduced the thickness of the uterine endometrium in PCOS mice. Our findings suggest that sustained high levels of progesterone during pregnancy can enhance ovarian reproductive endocrine capacity and improve endometrial function, thereby facilitating the recovery of postpartum menstrual cycles.