Clinical and biochemical discriminants between functional hypothalamic amenorrhoea (FHA) and polycystic ovary syndrome (PCOS)

Phylactou, Maria; Clarke, Sophie; Patel, Bijal; Baggaley, Caitlin; Jayasena, Channa N.; Kelsey, Tom; Comninos, Alexander N; Dhillo, Waljit S.; Abbara, Ali

doi:10.1111/cen.14402

Cited by 53 publications

(57 citation statements)

References 154 publications

(288 reference statements)

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“…Subsequent studies have confirmed the observation of elevated kisspeptin levels seen in PCOS. In a literature review by Tang et al [ 35 ] conducted in July 2018, twelve studies were found which considered serum kisspeptin levels in PCOS. Eight of the twelve studies found significantly higher serum levels in patients with PCOS.…”

Section: Kisspeptin and Pcosmentioning

confidence: 99%

Neuroendocrine Determinants of Polycystic Ovary Syndrome

Szeliga

Rudnicka

Maciejewska-Jeske

et al. 2022

IJERPH

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Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women and a major cause of anovulatory infertility. A diagnosis of PCOS is established based the presence of two out of three clinical symptoms, which are criteria accepted by the ESHRE/ASRM (European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine). Gonadotropin-releasing hormone (GnRH) is responsible for the release of luteinizing hormone, and follicle stimulating hormone from the pituitary and contributes a leading role in controlling reproductive function in humans. The goal of this review is to present the current knowledge on neuroendocrine determinations of PCOS. The role of such neurohormones as GnRH, and neuropeptides kisspeptin, neurokinin B, phoenixin-14, and galanin is discussed in this aspect. Additionally, different neurotransmitters (gamma-aminobutyric acid (GABA), glutamate, serotonin, dopamine, and acetylcholine) can also be involved in neuroendocrine etiopathogenesis of PCOS. Studies have shown a persistent rapid GnRH pulse frequency in women with PCOS present during the whole ovulatory cycle. Other studies have proved that patients with PCOS are characterized by higher serum kisspeptin levels. The observations of elevated serum kisspeptin levels in PCOS correspond with the hypothesis that overactivity in the kisspeptin system is responsible for hypothalamic-pituitary-gonadal axis overactivity. In turn, this causes menstrual disorders, hyperandrogenemia and hyperandrogenism. Moreover, abnormal regulation of Neurokinin B (NKB) is also suspected of contributing to PCOS development, while NKB antagonists are used in the treatment of PCOS leading to reduction in Luteinizing hormone (LH) concentration and total testosterone concentration. GnRH secretion is regulated not only by kisspeptin and neurokinin B, but also by other neurohormones, such as phoenixin-14, galanin, and Glucagon-like peptide-1 (GLP-1), that have favorable effects in counteracting the progress of PCOS. A similar process is associated with the neurotransmitters such as GABA, glutamate, serotonin, dopamine, and acetylcholine, as well as the opioid system, which may interfere with secretion of GnRH, and therefore, influence the development and severity of symptoms in PCOS patients. Additional studies are required to explain entire, real mechanisms responsible for PCOS neuroendocrine background.

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Section: Kisspeptin and Pcosmentioning

confidence: 99%

Neuroendocrine Determinants of Polycystic Ovary Syndrome

Szeliga

Rudnicka

Maciejewska-Jeske

et al. 2022

IJERPH

View full text Add to dashboard Cite

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“…( 5 ), the exclusion of other reasons for oligo-/amenorrhea is warranted in the definition criteria for both PCOS and FHA and there is no available test that is ultimately discriminating. Moreover, it has been mentioned that these diagnostic uncertainties also make the initial assignment to PCOS or FHA in studies more difficult ( 6 ). Thus, a precise definition of PCOS and FHA would be desirable in studies about this specific topic.…”

Section: Introductionmentioning

confidence: 99%

Polycystic Ovary Syndrome Phenotype D Versus Functional Hypothalamic Amenorrhea With Polycystic Ovarian Morphology: A Retrospective Study About a Frequent Differential Diagnosis

et al. 2022

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The two most frequent causes of secondary amenorrhea are polycystic ovary syndrome (PCOS) and functional hypothalamic amenorrhea (FHA). Despite several studies showing differences in hormonal profile between these groups, the differential diagnosis remains challenging, in particular between FHA women with polycystic ovarian morphology (FHA-PCOM) and PCOS patients without hyperandrogenism (phenotype D, PCOS-D). In a retrospective case-control study, 58 clearly defined patients with FHA-PCOM were compared to 58 PCOS-D patients, matched 1:1 for age and BMI. Significantly higher levels of LH, estradiol, testosterone, and a higher luteinizing hormone (LH): follicle stimulating hormone (FSH) ratio as well as lower sexual hormone binding globulin (SHBG) levels were found in PCOS-D patients (p< 0.05). Optimized cut-off values for the prediction of FHA-PCOM were calculated by the Youden index. The highest sensitivity was found for an estradiol serum level <37.5 pg/mL (84.5%, 95% confidence interval, CI: 72.6-92.6), whereas a LH : FSH ratio <0.96 had the highest specificity (94.8, 95% CI: 85.6-98.9). A linear discriminant analysis including testosterone, SHBG and LH was able to correctly classify 87.9% of FHA-PCOM patients (bootstrap 95% CI: 80.2 - 94.0%). In conclusion, this model including serological parameters could be an easy and reliable tool to distinguish between FHA-PCOM and PCOS-D patients, especially in situations where the clinical profile is not obvious.

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“…LH is measured routinely in clinical practice using an automated chemiluminescent immunoassay method and is the gold standard surrogate marker of GnRH. Furthermore, LH can be measured at frequent intervals (eg 10minutely) to assess GnRH/LH pulsatility, and accurate assessment of LH pulsatility could help facilitate diagnosis and treatment of patients presenting with reproductive endocrine disorders 9 . However, this is rarely done in clinical practice because it is resource-intensive, inconvenient for patients, and there is a lack of user-friendly methods for computational analysis of the LH data available to clinicians.…”

Section: Introductionmentioning

confidence: 99%

HormoneBayes: a novel Bayesian framework for the analysis of pulsatile hormone dynamics

Voliotis

Abbara

Prague

et al. 2022

Preprint

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The hypothalamus is the central regulator of reproductive hormone secretion. Pulsatile secretion of gonadotropin-releasing hormone (GnRH) is fundamental to physiological stimulation of the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Furthermore, GnRH pulsatility is altered in common reproductive disorders such as polycystic ovary syndrome (PCOS) and hypothalamic amenorrhea (HA). LH is measured routinely in clinical practice using an automated chemiluminescent immunoassay method and is the gold standard surrogate marker of GnRH. LH can be measured at frequent intervals (e.g., 10 minutely) to assess GnRH/LH pulsatility. However, this is rarely done in clinical practice because it is resource-intensive, and there is no user-friendly and accessible method for computational analysis of the LH data available to clinicians. Here we present hormoneBayes, a novel open-access Bayesian framework that can be easily applied to reliably analyze serial LH measurements to assess LH pulsatility. The framework utilizes parsimonious models to simulate hypothalamic signals that drive LH dynamics, together with state-of-the-art (sequential) Monte-Carlo methods to infer key parameters and latent hypothalamic dynamics. We show that this method provides estimates for key pulse parameters including inter-pulse interval, secretion and clearance rates and identifies LH pulses in line with the current gold-standard deconvolution method. We show that these parameters can distinguish LH pulsatility in different clinical contexts including in reproductive health and disease in men and women (e.g., healthy men, healthy women before and after menopause, women with HA or PCOS). A further advantage of hormoneBayes is that our mathematical approach provides a quantified estimation of uncertainty. Our framework will complement methods enabling real-time in-vivo hormone monitoring and therefore has the potential to assist the translation of personalized, data-driven, clinical care of patients presenting with conditions of reproductive hormone dysfunction.

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Clinical and biochemical discriminants between functional hypothalamic amenorrhoea (FHA) and polycystic ovary syndrome (PCOS)

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 53 publications

References 154 publications

Neuroendocrine Determinants of Polycystic Ovary Syndrome

Neuroendocrine Determinants of Polycystic Ovary Syndrome

Polycystic Ovary Syndrome Phenotype D Versus Functional Hypothalamic Amenorrhea With Polycystic Ovarian Morphology: A Retrospective Study About a Frequent Differential Diagnosis

HormoneBayes: a novel Bayesian framework for the analysis of pulsatile hormone dynamics

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