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Review
. 2022 Feb 13;11(4):647.
doi: 10.3390/cells11040647.

Progesterone Actions and Resistance in Gynecological Disorders

James A MacLean 2nd  1 , Kanako Hayashi  1
Affiliations
Review

Progesterone Actions and Resistance in Gynecological Disorders

James A MacLean 2nd et al. Cells. .

Abstract

Estrogen and progesterone and their signaling mechanisms are tightly regulated to maintain a normal menstrual cycle and to support a successful pregnancy. The imbalance of estrogen and progesterone disrupts their complex regulatory mechanisms, leading to estrogen dominance and progesterone resistance. Gynecological diseases are heavily associated with dysregulated steroid hormones and can induce chronic pelvic pain, dysmenorrhea, dyspareunia, heavy bleeding, and infertility, which substantially impact the quality of women's lives. Because the menstrual cycle repeatably occurs during reproductive ages with dynamic changes and remodeling of reproductive-related tissues, these alterations can accumulate and induce chronic and recurrent conditions. This review focuses on faulty progesterone signaling mechanisms and cellular responses to progesterone in endometriosis, adenomyosis, leiomyoma (uterine fibroids), polycystic ovary syndrome (PCOS), and endometrial hyperplasia. We also summarize the association with gene mutations and steroid hormone regulation in disease progression as well as current hormonal therapies and the clinical consequences of progesterone resistance.

Keywords: PCOS; adenomyosis; endometriosis; endometrium; progesterone; progesterone resistance.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Menstrual cycle. Steroid hormone-derived endometrial changes. Created with BioRender.com.
See this image and copyright information in PMC

References

    1. Graham J.D., Clarke C.L. Physiological action of progesterone in target tissues. Endocr. Rev. 1997;18:502–519. - PubMed
    1. Lydon J.P., DeMayo F.J., Funk C.R., Mani S.K., Hughes A.R., Montgomery C.A., Jr., Shyamala G., Conneely O.M., O’Malley B.W. Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Genes Dev. 1995;9:2266–2278. doi: 10.1101/gad.9.18.2266. - DOI - PubMed
    1. Patel B., Elguero S., Thakore S., Dahoud W., Bedaiwy M., Mesiano S. Role of nuclear progesterone receptor isoforms in uterine pathophysiology. Hum. Reprod. Update. 2015;21:155–173. doi: 10.1093/humupd/dmu056. - DOI - PMC - PubMed
    1. Kastner P., Krust A., Turcotte B., Stropp U., Tora L., Gronemeyer H., Chambon P. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J. 1990;9:1603–1614. doi: 10.1002/j.1460-2075.1990.tb08280.x. - DOI - PMC - PubMed
    1. Mulac-Jericevic B., Mullinax R.A., DeMayo F.J., Lydon J.P., Conneely O.M. Subgroup of reproductive functions of progesterone mediated by progesterone receptor-B isoform. Science. 2000;289:1751–1754. doi: 10.1126/science.289.5485.1751. - DOI - PubMed

Publication types

Supplementary concepts