The effects of weight loss on hypothalamic dysfunction in a woman with polycystic ovary syndrome (PCOS)

Kanyada Koysombat; Yeung Arthur C; Nyunt Sandhi W; Ambreen Qayum; Bijal Patel; Jovanna Tsoutsouki; Elisabeth Daniels; Megan Young; Tan Tricia M-M; Comninos Alexander N; Dhillo Waljit S; Ali Abbara

doi:10.1530/endoabs.109.P227

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Endocrine Abstracts (2025) 109 P227 | DOI: 10.1530/endoabs.109.P227

SFEBES2025 Poster Presentations Reproductive Endocrinology (22 abstracts)

The effects of weight loss on hypothalamic dysfunction in a woman with polycystic ovary syndrome (PCOS)

Kanyada Koysombat ^1,2 , Arthur C Yeung ¹ , Sandhi W Nyunt ^1,2 , Ambreen Qayum ^1,2 , Bijal Patel ^1,2 , Jovanna Tsoutsouki ¹ , Elisabeth Daniels ¹ , Megan Young ¹ , Tricia M-M Tan ^1,2,3 , Alexander N Comninos ^1,2 , Waljit S Dhillo ^1,2 & Ali Abbara ^1,2

Author affiliations

¹Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom; ²Department of Endocrinology, Imperial College Healthcare NHS Trust, London, London, United Kingdom; ³North West London Pathology, London, United Kingdom

Background: Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy in reproductive-aged women. Hypothalamic neuroendocrine dysfunction contributes to the pathogenesis of PCOS. Specifically, gonadotrophin releasing hormone (GnRH) activity is increased, favouring luteinising hormone (LH) secretion, leading to ovarian hyperandrogenism and oligo/anovulation. Herein, we describe changes in reproductive hormone concentrations, LH pulse frequency, and the response to kisspeptin (used to probe hypothalamic GnRH function) in a woman with PCOS and obesity, before and after weight-loss via bariatric surgery.

Case: A 23-year-old woman with PCOS achieved 30 kg weight-loss (BMI 39 to 25 kg/m²) following sleeve gastrectomy. Three months after bariatric surgery, she regained spontaneous menstrual cyclicity with improvements in her cycle length (from 139-420 days pre-operatively to 42-84 days post-operatively). Changes in her endocrine profile post progesterone-induced withdrawal bleed are presented in Table 1. Intriguingly, her LH pulse frequency, reduced from 1 to 0.5 pulse/hour post-bariatric surgery, aligning more closely to a physiological follicular phase LH pulse frequency. Pre-operative kisspeptin-54 stimulation resulted in a peak LH response of 12.9 IU/l, which was reduced to 6.6 IU/L post-operatively.

Table 1: Pre- and post-operative reproductive hormones
	Pre-bariatric surgery	Post-bariatric surgery	Reference range
Luteinising hormone (IU/l)	9.6	1.9	-
Follicle stimulating hormone (IU/l)	4.5	4.5	0.6-9.0
Testosterone (nmol/l)	1.9	1.0	0.0-2.0
Sex hormone binding globulin (nmol/l)	11	29	30-100
Anti-Müllerian hormone (pmol/l)	64.7	40.7	-

Discussion: PCOS is associated with an abnormal increase in hypothalamic GnRH function. Obesity exacerbates PCOS, but is associated with decreased LH concentrations. In this woman with PCOS and obesity, increased LH pulse frequency normalised with weight loss. Additionally, her increased gonadotrophin response to kisspeptin also normalised, consistent with an obesity-related component of her hypothalamic dysfunction. This case highlights the potential of kisspeptin in evaluating the impact of obesity and neuroendocrine dysfunction in women with PCOS.