McCartney, C. R., Eagleson, C. A., & Marshall, J. C. (2002). Regulation of gonadotropin secretion: implications for polycystic ovary syndrome. Seminars in Reproductive Medicine, 20(4), 317-326. https://doi.org/10.1055/s-2002-36706
McCartney CR, Eagleson CA, Marshall JC. Regulation of gonadotropin secretion: implications for polycystic ovary syndrome. Semin Reprod Med. 2002;20(4):317-326. doi:10.1055/s-2002-36706
McCartney, Christopher R., et al. "Regulation of gonadotropin secretion: implications for polycystic ovary syndrome." Seminars in Reproductive Medicine, vol. 20, no. 4, 2002, pp. 317-326.
PCOS involves a GnRH pulse generator that resists progesterone
A 2002 review of polycystic ovary syndrome (PCOS) finds that the brain's pulse generator responds weakly to progesterone. As a result, its pulses stay persistently rapid. Luteinizing hormone (LH) is commonly high, and follicle-stimulating hormone (FSH) is typically in the lower follicular range.
Key Findings
Women with PCOS commonly have raised luteinizing hormone (LH), and follicle-stimulating hormone (FSH) is typically in the lower follicular range.
In PCOS, LH pulses stay persistently rapid, at approximately one per hour, which the authors take by inference to mirror the pace of gonadotropin-releasing hormone (GnRH) pulses.
The GnRH pulse generator in PCOS is less responsive to the slowing effect of ovarian steroids, with progesterone singled out.
The androgen receptor antagonist flutamide reverses the reduced responsiveness, suggesting that elevated androgen levels may alter how the pulse generator responds.
The pulse generator slows only at higher progesterone levels in PCOS, leaving FSH production short and ovarian androgens under constant LH drive.
Interpretation
The record holds the abstract of a 2002 review article, so the summary reflects the authors' conclusions and reports no new study data. The authors state that the cause of these brain and hormone changes remains unclear. For puberty, they propose that in girls with high androgen levels who go on to develop PCOS the nighttime rise in ovarian steroids may not be adequate to slow the pulse frequency. LH pulses may then stay rapid, FSH output may be impaired and follicles may develop inadequately.
RRM Context
The syndrome also carries the newer official label PMOS (Polyendocrine Metabolic Ovarian Syndrome), and PCOS remains the term in this paper. Failure to ovulate in PCOS has a hormonal mechanism in the signaling between brain and ovary. Restorative reproductive medicine starts from that root-cause question: why ovulation fails. Cycle charting records the cycle pattern behind hormone findings like these.
Our editorial summary of this paper, not the article's abstract.
Abstract
Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism and chronic anovulation. Although the etiology of PCOS is unknown, perturbations of gonadotropin secretion are one of the hallmarks of this disorder. In normal menstrual physiology, the monotropic rise of plasma follicle-stimulating hormone (FSH) during the luteal-follicular transition is critical for follicular development and subsequent ovulation. One of the mechanisms by which FSH is differentially synthesized involves the luteal slowing of gonadotropin-releasing hormone (GnRH) pulse frequency by ovarian steroids. In PCOS, plasma leutinizing hormone (LH) is commonly increased, FSH is typically in the lower follicular range, and LH (and by inference GnRH) pulse frequency is persistently rapid at approximately one LH pulse per hour. The etiology of the neuroendocrine abnormalities in PCOS remain unclear; however, recent studies have revealed decreased sensitivity of the GnRH pulse generator to inhibition by ovarian steroids, particularly progesterone. This abnormality is reversed by the androgen receptor antagonist flutamide, suggesting that elevated androgen levels may alter the sensitivity of the hypothalamic GnRH pulse generator to steroid inhibition and lead to enhanced LH secretion. As such, women with PCOS require higher levels of progesterone to slow the frequency of GnRH pulse secretion, resulting in inadequate FSH synthesis and persistent LH stimulation of ovarian androgens. The decreased sensitivity of the GnRH pulse generator may help to explain the genesis of PCOS during puberty. In normal early puberty, sleep-entrained increases in LH stimulate ovarian steroids, which subsequently suppress LH frequency and amplitude during the subsequent day. In hyperandrogenemic girls destined to develop PCOS, this nocturnal increase in ovarian steroids may not be adequate to suppress the GnRH pulse generator, leading to a persistently rapid LH pulse frequency, impaired FSH production, and inadequate follicular development.
