Progesterone Suppression of Luteinizing Hormone Pulse Frequency in Adolescent Girls With Hyperandrogenism: Effects of Metformin

Lundgren, Jessica A; Kim, Suhee; Solorzano, Christine M. Burt; McCartney, Christopher R.; Marshall, John C.

doi:10.1210/jc.2017-02068

Cited by 10 publications

(3 citation statements)

References 29 publications

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“…The decrease in the expression of progesterone receptor was observed [ 78 ]. This finding of the impaired progesterone feedback was shown in the study, in which the women afflicted by PCOS required higher levels of progesterone to decrease the LH level, as compared to the women without PCOS [ 79 ].…”

Section: Potential Drug Targets and Active Substances In Novel Thementioning

confidence: 63%

In Search of New Therapeutics—Molecular Aspects of the PCOS Pathophysiology: Genetics, Hormones, Metabolism and Beyond

Wawrzkiewicz-Jałowiecka

Kowalczyk

Trybek

et al. 2020

IJMS

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In a healthy female reproductive system, a subtle hormonal and metabolic dance leads to repetitive cyclic changes in the ovaries and uterus, which make an effective ovulation and potential implantation of an embryo possible. However, that is not so in the case of polycystic ovary syndrome (PCOS), in which case the central mechanism responsible for entraining hormonal and metabolic rhythms during the menstrual cycle is notably disrupted. In this review we provide a detailed description of the possible scenario of PCOS pathogenesis. We begin from the analysis of how a set of genetic disorders related to PCOS leads to particular malfunctions at a molecular level (e.g., increased enzyme activities of cytochrome P450 (CYP) type 17A1 (17α-hydroxylase), 3β-HSD type II and CYP type 11A1 (side-chain cleavage enzyme) in theca cells, or changes in the expression of aquaporins in granulosa cells) and discuss further cellular- and tissue-level consequences (e.g., anovulation, elevated levels of the advanced glycation end products in ovaries), which in turn lead to the observed subsequent systemic symptoms. Since gene-editing therapy is currently out of reach, herein special emphasis is placed on discussing what kinds of drug targets and which potentially active substances seem promising for an effective medication, acting on the primary causes of PCOS on a molecular level.

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Section: Potential Drug Targets and Active Substances In Novel Thementioning

confidence: 63%

In Search of New Therapeutics—Molecular Aspects of the PCOS Pathophysiology: Genetics, Hormones, Metabolism and Beyond

Wawrzkiewicz-Jałowiecka

Kowalczyk

Trybek

et al. 2020

IJMS

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“…The PCOS group in our study was under treatment with metformin. It has been shown that metformin improves not only insulin resistance but also biochemical hyperandrogenemia [40]. No data exist regarding the effect of oral contraceptives on the body composition of lean PCOS patients, but in menopausal females, OCs seem to induce muscle anabolism [41].…”

Section: Discussionmentioning

confidence: 99%

Lean Women on Metformin and Oral Contraceptives for Polycystic Ovary Syndrome Demonstrate a Dehydrated Osteosarcopenic Phenotype: A Pilot Study

et al. 2019

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Scarce data exist on the body composition of lean women with polycystic ovary syndrome (PCOS) on treatment with metformin and oral contraceptives (OCs). Thirty-four lean (body mass index 18.5–24.9 kg/m2) women (17 with PCOS on metformin and OCs treatment for six months and 17 controls) aged 18–40 years were assessed for body composition parameters (fat, muscle, glycogen, protein masses, bone masses, and body water compartments) and phase angles. PCOS patients demonstrated lower muscle, glycogen and protein masses (U = 60, p = 0.003), along with a lower bone mineral content and mass (U = 78, p = 0.021; U = 74, p = 0.014) than their healthy counterparts, while total and abdominal fat masses were similar between the two groups. PCOS patients also exhibited increased extracellular body water (U = 10, p < 0.001) and decreased intracellular water, compatible with low-grade inflammation and cellular dehydration. Key differences in body composition between women with PCOS and controls demonstrated an osteosarcopenic body composition phenotype in PCOS patients. A confirmation of these findings in larger studies may render osteosarcopenia management a targeted adjunct therapy in women with PCOS.

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“…Reduced hypothalamic sensitivity to progesterone negative feedback on LH secretion also is a hallmark of PCOS women (Chhabra et al 2005) and is similarly restored with flutamide (Eagleson et al 2000, Chhabra et al 2005. Comparable neuroendocrine abnormalities are found in adolescent hyperandrogenic girls, likely representing a precursor to adult PCOS (Lundgren et al 2018). Moreover, PCOS women show a sexually dimorphic pattern of exaggerated early LH responsiveness to GnRH analog that more closely resembles that of men or women with congenital adrenal virilizing disorders (e.g., classical CAH and adrenal virilizing carcinoma) than normal women (Rosenfield et al 1990, Barnes et al 1994.…”

Section: Neuroendocrine Dysfunctionmentioning

confidence: 99%

Mechanisms of intergenerational transmission of polycystic ovary syndrome

et al. 2020

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Developmental origins of adult disease (DoHAD) refers to critical gestational ages during human fetal development and beyond when the endocrine metabolic status of the mother can permanently program the physiology and/or morphology of the fetus, modifying its susceptibility to disease after birth. The aim of this review is to address how DoHAD plays an important role in the phenotypic expression of polycystic ovary syndrome (PCOS), the most common endocrinopathy of women characterized by hyperandrogenism, oligo-anovulation and polycystic ovarian morphology. Clinical studies of PCOS women are integrated with findings from relevant animal models to show how intergenerational transmission of these central components of PCOS are programmed through an altered maternal endocrine–metabolic environment that adversely affects the female fetus and long-term offspring health. Prenatal testosterone treatment in monkeys and sheep have been particularly crucial in our understanding of developmental programming of PCOS because organ system differentiation in these species, as in humans, occurs during fetal life. These animal models, along with altricial rodents, produce permanent PCOS-like phenotypes variably characterized by LH hypersecretion from reduced steroid-negative feedback, hyperandrogenism, ovulatory dysfunction, increased adiposity, impaired glucose-insulin homeostasis and other metabolic abnormalities. The review concludes that DoHAD underlies the phenotypic expression of PCOS through an altered maternal endocrine–metabolic environment that can induce epigenetic modifications of fetal genetic susceptibility to PCOS after birth. It calls for improved maternal endocrine–metabolic health of PCOS women to lower their risks of pregnancy-related complications and to potentially reduce intergenerational susceptibility to PCOS and its metabolic derangements in offspring.

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Progesterone Suppression of Luteinizing Hormone Pulse Frequency in Adolescent Girls With Hyperandrogenism: Effects of Metformin

Abstract: Short-term metformin use improved biochemical hyperandrogenemia, but did not improve hypothalamic sensitivity to P4 suppression, in adolescent girls.

Cited by 10 publications

References 29 publications

In Search of New Therapeutics—Molecular Aspects of the PCOS Pathophysiology: Genetics, Hormones, Metabolism and Beyond

In Search of New Therapeutics—Molecular Aspects of the PCOS Pathophysiology: Genetics, Hormones, Metabolism and Beyond

Lean Women on Metformin and Oral Contraceptives for Polycystic Ovary Syndrome Demonstrate a Dehydrated Osteosarcopenic Phenotype: A Pilot Study

Mechanisms of intergenerational transmission of polycystic ovary syndrome

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