M�llerian-inhibiting substance in women with polycystic ovary syndrome: Relationship with hormonal and metabolic characteristics

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity, and insulin resistance. However, its etiology is unclear, and its management is often unsatisfactory or requires a diversified approach. Here, we describe a new rat PCOS model, the first to exhibit both ovarian and metabolic characteristics of the syndrome. Female rats received the nonaromatizable androgen dihydrotestosterone (DHT) or the aromatase inhibitor letrozole by continuous administration, beginning before puberty, to activate androgen receptors. Adult DHT rats had irregular cycles, polycystic ovaries characterized by cysts formed from atretic follicles, and a diminished granulosa layer. They also displayed metabolic features, including increased body weight, increased body fat, and enlarged mesenteric adipocytes, as well as elevated leptin levels and insulin resistance. All letrozole rats were anovulatory and developed polycystic ovaries with structural changes strikingly similar to those in human PCOS. Our findings suggest that the formation of a “hyperplastic” theca interna reflects the inclusion of luteinized granulosa cells in the cyst wall rather than true hyperplasia. We conclude that the letrozole model is suitable for studies of the ovarian features of human PCOS, while the DHT model is suitable for studies of both ovarian and metabolic features of the syndrome.

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Clinical and metabolic characteristics of Turkish adolescents with polycystic ovary syndrome

Journal of Obstetrics and Gynaecology ◽

10.1080/01443615.2017.1345875 ◽

2017 ◽

Vol 38 (2) ◽

pp. 236-240 ◽

Cited By ~ 3

Author(s):

Seda Ates ◽

Serdar Aydın ◽

Pinar Ozcan ◽

Zeynep Soyman ◽

Ayse Filiz Gokmen Karasu ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Metabolic Characteristics

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Association between menstrual cycle irregularities and endocrine and metabolic characteristics of the polycystic ovary syndrome

Acta Endocrinologica ◽

10.1530/eje-12-0655 ◽

2013 ◽

Vol 168 (2) ◽

pp. 145-152 ◽

Cited By ~ 15

Author(s):

Dimitrios Panidis ◽

Konstantinos Tziomalos ◽

Panagiotis Chatzis ◽

Efstathios Papadakis ◽

Dimitrios Delkos ◽

...

Keyword(s):

Menstrual Cycle ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Secondary Amenorrhea ◽

Insulin Resistant ◽

Metabolic Characteristics ◽

Increased Risk ◽

Group D

ObjectiveInsulin resistance (IR) is frequent in polycystic ovary syndrome (PCOS) and contributes to the increased risk for type 2 diabetes mellitus and cardiovascular disease of this population. Several markers of IR are used but most are expensive or have limited sensitivity and specificity. Preliminary data suggest that the menstrual cycle pattern correlates with IR in PCOS but existing studies are small. We aimed to assess the relationship between the type of menstrual cycle irregularities and IR in PCOS.DesignProspective study.MethodsWe studied 1285 women with PCOS, divided according to the menstrual cycle pattern.ResultsPatients with isolated secondary amenorrhea and those with secondary amenorrhea alternating with regular menstrual cycles were more insulin resistant than patients with regular cycles (Group D). Patients with isolated oligomenorrhea were also more insulin resistant than Group D. However, patients with oligomenorrhea alternating with regular cycles, secondary amenorrhea, or polymenorrhea had comparable levels of markers of IR with Group D. Moreover, patients with oligomenorrhea alternating with regular cycles were less insulin resistant than patients with secondary amenorrhea alternating with regular cycles. Finally, patients with isolated polymenorrhea and those with polymenorrhea alternating with regular cycles had comparable levels of markers of IR with Group D.ConclusionsAmenorrhea is associated with more pronounced IR in PCOS, and oligomenorrhea portends a less excessive risk for IR than amenorrhea whereas polymenorrhea appears to be even more benign metabolically. Therefore, the type of menstrual cycle abnormality appears to represent a useful tool for identifying a more adverse metabolic profile in PCOS.

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Effects of Metformin on Reproductive, Endocrine, and Metabolic Characteristics of Female Offspring in a Rat Model of Letrozole-induced Polycystic Ovarian Syndrome With Insulin Resistant

10.21203/rs.3.rs-122468/v1 ◽

2020 ◽

Author(s):

Yidong Xie ◽

Li Xiao ◽

Xiaohan Shi ◽

Yifan Zhao ◽

Xiaohong Li ◽

...

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Rat Model ◽

Wistar Rats ◽

Polycystic Ovary ◽

Female Offspring ◽

Ovary Syndrome ◽

Metabolic Characteristics ◽

Reproductive Endocrine ◽

The Impact

Abstract Background: Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder that has many characteristic features including hyperandrogenemia, insulin resistance and obesity. The beneficial effects of metformin on reproduction, metabolism and endocrine, especially with the capacity to ameliorate insulin resistance (IR) in polycystic ovary syndrome (PCOS), place it as a good alternative for its widely prescribed, but its association with PCOS offspring remains uncertain. We aim to investigate the impact of metformin on reproductive, endocrine and metabolic characteristics in female offspring born to letrozole-induced PCOS-IR rats.Methods: 45 female wistar rats were implanted with letrozole-continuous-release pellets or placebo, subsequently treated with metformin or vehicle control, then mated with healthy male wistar rats. Estrous cycle, endocrine hormone profile, fasting insulin measurements and glucose tolerance test have been investigated and the expression of INSR in pancreas, FSHR and LHCGR in ovaries have been analyzed with Quantitative Real-time Polymerase Chain Reaction and Western Blotting assay.Results: Decreased conception rate and increased multiple pregnancy rates were found in PCOS-IR rats, which significantly improved after metformin treatment. Metformin significantly decreased the risk of body weight gain and increased INSR expression of pancreas in female F1 offspring in PCOS-IR rats. Decreased FSHR and increased LHCGR expressions in ovary were observed in female F1 rats of PCOS-IR and PCOS-IR+Met group. Nevertheless, there were no significant differences of INSR, FSHR and LHCGR expressions in female F2 offspring of PCOS-IR rats, as well as other PCOS phenotypes.Conclusions: The current study indicates that widespread reproductive, endocrine and metabolic changes in letrozole induced PCOS-IR rat model, but those PCOS phenotypes could not be inherit to offspring generations stably. Metformin may contribute to improve obesity, hyperinsulinemia and insulin resistance of female F1 offspring in PCOS-IR. The results of this study can be used as a theoretical basis for supporting metformin-using in the treatment of PCOS-IR patients.

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