Progesterone Action on Endometrium of PCOS

Summary

Objective: To study the influence of metabolic factors on the action of progesterone on the endometrium of women with PCOS. Design: A prospective open-label clinical trial. Setting: Participants were recruited from an outpatient reproductive endocrinology clinic at an academic tertiary medical care center from 2014 to 2019. Subjects: To assess the sole effect of progesterone (P4) on the endometrium we studied amenorrheic (cycles\> 90 days) women with PCOS (n=23), comparing them to healthy eumenorrheic control women ( n=13). Intervention(s): All subjects underwent an endometrial biopsy (EB) in the follicular phase of the first study cycle. They were then treated with micronized P4 (400 mg/day x 10 days intravaginally) from days 14-28 of the cycle, and a second EB was performed between days 20-24 of the cycle (second phase). Main Outcome Measure(s): EB samples were analyzed under light microscopy for histomorphometric analysis.

Timeline

Start

2014-02-10

Primary completion

2014-09-10

Completion

2019-04-21

Publications

• Background Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, Piltonen T, Norman RJ; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018 Sep 1;33(9):1602-1618. doi: 10.1093/humrep/dey256.
• Background Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF; Androgen Excess Society. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab. 2006 Nov;91(11):4237-45. doi: 10.1210/jc.2006-0178. Epub 2006 Aug 29.
• Background Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF; Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009 Feb;91(2):456-88. doi: 10.1016/j.fertnstert.2008.06.035. Epub 2008 Oct 23.
• Background Trivax B, Azziz R. Diagnosis of polycystic ovary syndrome. Clin Obstet Gynecol. 2007 Mar;50(1):168-77. doi: 10.1097/GRF.0b013e31802f351b.
• Background Giudice LC. Endometrium in PCOS: Implantation and predisposition to endocrine CA. Best Pract Res Clin Endocrinol Metab. 2006 Jun;20(2):235-44. doi: 10.1016/j.beem.2006.03.005.
• Background Slayden OD, Nayak NR, Burton KA, Chwalisz K, Cameron ST, Critchley HO, Baird DT, Brenner RM. Progesterone antagonists increase androgen receptor expression in the rhesus macaque and human endometrium. J Clin Endocrinol Metab. 2001 Jun;86(6):2668-79. doi: 10.1210/jcem.86.6.7606.
• Background Ochoa-Bernal MA, Fazleabas AT. Physiologic Events of Embryo Implantation and Decidualization in Human and Non-Human Primates. Int J Mol Sci. 2020 Mar 13;21(6):1973. doi: 10.3390/ijms21061973.
• Background Sharpe A, Morley LC, Tang T, Norman RJ, Balen AH. Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2019 Dec 17;12(12):CD013505. doi: 10.1002/14651858.CD013505.
• Background Walls ML, Hunter T, Ryan JP, Keelan JA, Nathan E, Hart RJ. In vitro maturation as an alternative to standard in vitro fertilization for patients diagnosed with polycystic ovaries: a comparative analysis of fresh, frozen and cumulative cycle outcomes. Hum Reprod. 2015 Jan;30(1):88-96. doi: 10.1093/humrep/deu248. Epub 2014 Oct 29.
• Background Simoes RS, Soares JM Jr, Simoes MJ, Nader HB, Baracat MCP, Maciel GAR, Serafini PC, Azziz R, Baracat EC. Small leucine-rich proteoglycans (SLRPs) in the endometrium of polycystic ovary syndrome women: a pilot study. J Ovarian Res. 2017 Aug 8;10(1):54. doi: 10.1186/s13048-017-0349-9.
• Background Munro MG, Critchley HOD, Fraser IS; FIGO Menstrual Disorders Committee. The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions. Int J Gynaecol Obstet. 2018 Dec;143(3):393-408. doi: 10.1002/ijgo.12666. Epub 2018 Oct 10.
• Background Lai TH, Zhao Y, Shih IeM, Ho CL, Bankowski B, Vlahos N. Expression of L-selectin ligands in human endometrium during the implantation window after controlled ovarian stimulation for oocyte donation. Fertil Steril. 2006 Mar;85(3):761-3. doi: 10.1016/j.fertnstert.2005.08.023.
• Background Quezada S, Avellaira C, Johnson MC, Gabler F, Fuentes A, Vega M. Evaluation of steroid receptors, coregulators, and molecules associated with uterine receptivity in secretory endometria from untreated women with polycystic ovary syndrome. Fertil Steril. 2006 Apr;85(4):1017-26. doi: 10.1016/j.fertnstert.2005.09.053. Epub 2006 Mar 9.
• Background Qiao J, Wang L, Li R, Zhang X. Microarray evaluation of endometrial receptivity in Chinese women with polycystic ovary syndrome. Reprod Biomed Online. 2008 Sep;17(3):425-35. doi: 10.1016/s1472-6483(10)60228-3.
• Background Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Consensus on women's health aspects of polycystic ovary syndrome (PCOS). Hum Reprod. 2012 Jan;27(1):14-24. doi: 10.1093/humrep/der396. Epub 2011 Dec 5.
• Background Griukova A, Deryabin P, Shatrova A, Burova E, Severino V, Farina A, Nikolsky N, Borodkina A. Molecular basis of senescence transmitting in the population of human endometrial stromal cells. Aging (Albany NY). 2019 Nov 5;11(21):9912-9931. doi: 10.18632/aging.102441. Epub 2019 Nov 5.
• Background Apparao KB, Lovely LP, Gui Y, Lininger RA, Lessey BA. Elevated endometrial androgen receptor expression in women with polycystic ovarian syndrome. Biol Reprod. 2002 Feb;66(2):297-304. doi: 10.1095/biolreprod66.2.297.
• Background Cheung AP. Ultrasound and menstrual history in predicting endometrial hyperplasia in polycystic ovary syndrome. Obstet Gynecol. 2001 Aug;98(2):325-31. doi: 10.1016/s0029-7844(01)01432-6.
• Background Maliqueo M, Clementi M, Gabler F, Johnson MC, Palomino A, Sir-Petermann T, Vega M. Expression of steroid receptors and proteins related to apoptosis in endometria of women with polycystic ovary syndrome. Fertil Steril. 2003 Sep;80 Suppl 2:812-9. doi: 10.1016/s0015-0282(03)00987-7.
• Background Heijnen EM, Eijkemans MJ, Hughes EG, Laven JS, Macklon NS, Fauser BC. A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome. Hum Reprod Update. 2006 Jan-Feb;12(1):13-21. doi: 10.1093/humupd/dmi036. Epub 2005 Aug 25.
• Results Lopes IM, Baracat MC, Simoes Mde J, Simoes RS, Baracat EC, Soares JM Jr. Endometrium in women with polycystic ovary syndrome during the window of implantation. Rev Assoc Med Bras (1992). 2011 Nov-Dec;57(6):702-9. doi: 10.1590/s0104-42302011000600020. English, Portuguese.
• Results de Medeiros SF, Yamamoto MMW, Souto de Medeiros MA, Barbosa BB, Soares JM, Baracat EC. Changes in clinical and biochemical characteristics of polycystic ovary syndrome with advancing age. Endocr Connect. 2020 Feb;9(2):74-89. doi: 10.1530/EC-19-0496.
• Results Baracat MC, Serafini PC, Simoes Rdos S, Maciel GA, Soares JM Jr, Baracat EC. Systematic review of cell adhesion molecules and estrogen receptor expression in the endometrium of patients with polycystic ovary syndrome. Int J Gynaecol Obstet. 2015 Apr;129(1):1-4. doi: 10.1016/j.ijgo.2014.10.022. Epub 2014 Dec 18.
• Results Lopes IM, Maganhin CC, Oliveira-Filho RM, Simoes RS, Simoes MJ, Iwata MC, Baracat EC, Soares JM Jr. Histomorphometric Analysis and Markers of Endometrial Receptivity Embryonic Implantation in Women With Polycystic Ovary Syndrome During the Treatment With Progesterone. Reprod Sci. 2014 Jul;21(7):930-938. doi: 10.1177/1933719113519169. Epub 2014 Jan 23.
• Results Ejzenberg D, Simoes Mde J, Pinheiro W, Soares JM Junior, Serafini PC, Baracat EC. Blind aspiration biopsy versus a guided hysteroscopic technique for investigation of the endometrium in infertile women. Histol Histopathol. 2016 Sep;31(9):981-6. doi: 10.14670/HH-11-725. Epub 2016 Jan 25.
• Results Ejzenberg D, Gomes TJO, Monteleone PAA, Serafini PC, Soares-Jr JM, Baracat EC. Prognostic factors for pregnancy after intrauterine insemination. Int J Gynaecol Obstet. 2019 Oct;147(1):65-72. doi: 10.1002/ijgo.12898. Epub 2019 Jul 23.
• Results Savaris RF, Groll JM, Young SL, DeMayo FJ, Jeong JW, Hamilton AE, Giudice LC, Lessey BA. Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles. J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• Results Giordano MV, Giordano LA, Gomes RC, Simoes RS, Nader HB, Giordano MG, Baracat EC, Soares Junior JM. The evaluation of endometrial sulfate glycosaminoglycans in women with polycystic ovary syndrome. Gynecol Endocrinol. 2015 Apr;31(4):278-81. doi: 10.3109/09513590.2014.989980. Epub 2014 Dec 1.

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