Circulating Anti-Müllerian hormone in a cohort-study of women with severe obesity with and without polycystic ovary syndrome and the effect of a one-year weight loss intervention

Josefin Kataoka, Ingrid Larsson, Eva Lindgren, Li Oskarson Kindstrand, Johanna Schmidt, Elisabet Stener-Victorin, Josefin Kataoka, Ingrid Larsson, Eva Lindgren, Li Oskarson Kindstrand, Johanna Schmidt, Elisabet Stener-Victorin

Abstract

Background: Women with polycystic ovary syndrome (PCOS) have high circulating anti-Müllerian hormone (AMH) levels which is correlated with antral follicle count and polycystic ovarian morphology and negatively correlated with body mass index (BMI). Moreover, diet-induced weight loss in women with PCOS and overweight or obesity, reduce or normalize AMH-levels. There is, however, no previous study investigating the circulating AMH levels in women with severe obesity and how a structured diet-induced weight loss program affects circulating AMH levels in these women. Therefore, this study aims to investigate circulating AMH levels in a population of women with severe obesity (BMI ≥ 35 kg/m2) with and without PCOS, as diagnosed by the NIH-criteria, and to investigate the effect of a one-year weight loss program with a very low-energy diet (VLED) on circulating levels of AMH.

Methods: In a prospective cohort-study, were 246 women with severe obesity were screened for PCOS diagnosis with the NIH-criteria, circulating AMH and anthropometry were measured at baseline and after a 12-month weight loss intervention with very low-energy diet (VLED).

Results: Mean BMI was 39.9 ± 4.7 (PCOS), 39.6 ± 4.3 (non-PCOS) P = 0.960. Circulating AMH was higher in women with PCOS (5.47 ± 4.89 µg/L) compared with non-PCOS (2.66 ± 3.71 µg/L) P < 0.001 and was positively correlated with circulating total testosterone in both groups. Next, we performed ROC-analyses, and show that circulating AMH could not discriminate women with PCOS and severe obesity from non-PCOS women with severe obesity. Finally, a one-year weight reduction program does not affect circulating AMH levels despite significant weight loss neither in women with PCOS, nor without PCOS and severe obesity.

Conclusion: Women with severe obesity and PCOS have elevated levels of circulating AMH compared to women without the syndrome. AMH-levels could not discriminate women with PCOS from non-PCOS because of low sensitivity and specificity. Significant weight loss was not associated with changes in circulating AMH levels, neither in women with, nor without PCOS and severe obesity. These results imply that in women with severe obesity, a greater weight loss may be needed to improve reproductive features, independent of PCOS diagnosis.

Trial registration number: Clinical trial.gov: NCT01319162.

Keywords: Anti-Müllerian hormone; Polycystic ovary syndrome; Severe obesity; Weight loss.

Conflict of interest statement

The authors have no conflict or competing interests to disclose.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Circulating levels of AMH in women with severe obesity with PCOS (n = 63) and without PCOS (n = 183) at baseline
Fig. 2
Fig. 2
Circulating levels of AMH in women with severe obesity with PCOS (n = 19) and without PCOS (n = 64) did not change from before to after intervention
Fig. 3
Fig. 3
ROC curves for the detection of PCOS using circulating levels of free Testosterone (f-T) and AMH (anti-müllerian hormone)

References

    1. Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod (Oxford England) 2016;31(12):2841–55.
    1. March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod (Oxford England) 2010;25(2):544–51.
    1. Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2010;16(4):347–63.
    1. Schmidt J, Landin-Wilhelmsen K, Brannstrom M, Dahlgren E. Cardiovascular disease and risk factors in PCOS women of postmenopausal age: a 21-year controlled follow-up study. J Clin Endocrinol Metab. 2011;96(12):3794–803.
    1. Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care. 1999;22(1):141–6.
    1. Kataoka J, Larsson I, Björkman S, Eliasson B, Schmidt J, Stener-Victorin E. Prevalence of polycystic ovary syndrome in women with severe obesity - Effects of a structured weight loss programme. Clin Endocrinol (Oxf) 2019;91(6):750–8.
    1. Cook CL, Siow Y, Brenner AG, Fallat ME. Relationship between serum mullerian-inhibiting substance and other reproductive hormones in untreated women with polycystic ovary syndrome and normal women. Fertil Steril. 2002;77(1):141–6.
    1. Calzada M, López N, Noguera JA, Mendiola J, Hernández AI, Corbalán S, et al. AMH in combination with SHBG for the diagnosis of polycystic ovary syndrome. J Obstet Gynaecol. 2019;39(8):1130–6.
    1. Lin YH, Chiu WC, Wu CH, Tzeng CR, Hsu CS, Hsu MI. Antimüllerian hormone and polycystic ovary syndrome. Fertil Steril. 2011;96(1):230–5.
    1. Cimino I, Casoni F, Liu X, Messina A, Parkash J, Jamin SP, et al. Novel role for anti-Müllerian hormone in the regulation of GnRH neuron excitability and hormone secretion. Nat Commun. 2016;7:10055.
    1. Piouka A, Farmakiotis D, Katsikis I, Macut D, Gerou S, Panidis D. Anti-Mullerian hormone levels reflect severity of PCOS but are negatively influenced by obesity: relationship with increased luteinizing hormone levels. Am J Physiol Endocrinol metabolism. 2009;296(2):E238-43.
    1. Sova H, Unkila-Kallio L, Tiitinen A, Hippeläinen M, Perheentupa A, Tinkanen H, et al. Hormone profiling, including anti-Müllerian hormone (AMH), for the diagnosis of polycystic ovary syndrome (PCOS) and characterization of PCOS phenotypes. Gynecol Endocrinol. 2019;35(7):595–600.
    1. Pigny P, Jonard S, Robert Y, Dewailly D. Serum anti-Mullerian hormone as a surrogate for antral follicle count for definition of the polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91(3):941–5.
    1. Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod (Oxford England) 2018;33(9):1602–18.
    1. Lefebvre T, Dumont A, Pigny P, Dewailly D. Effect of obesity and its related metabolic factors on serum anti-Müllerian hormone concentrations in women with and without polycystic ovaries. Reprod Biomed Online. 2017;35(3):325–30.
    1. Freeman EW, Gracia CR, Sammel MD, Lin H, Lim LC, Strauss JF. Association of anti-mullerian hormone levels with obesity in late reproductive-age women. Fertil Steril. 2007;87(1):101–6.
    1. Moy V, Jindal S, Lieman H, Buyuk E. Obesity adversely affects serum anti-mullerian hormone (AMH) levels in Caucasian women. J Assist Reprod Genet. 2015;32(9):1305–11.
    1. Bernardi LA, Carnethon MR, de Chavez PJ, Ikhena DE, Neff LM, Baird DD, et al. Relationship between obesity and anti-Müllerian hormone in reproductive-aged African American women. Obes (Silver Spring Md) 2017;25(1):229–35.
    1. Casadei L, Fanisio F, Sorge RP, Collamarini M, Piccolo E, Piccione E. The diagnosis of PCOS in young infertile women according to different diagnostic criteria: the role of serum anti-Müllerian hormone. Arch Gynecol Obstet. 2018;298(1):207–15.
    1. Skałba P, Cygal A, Madej P, Dąbkowska-Huć A, Sikora J, Martirosian G, et al. Is the plasma anti-Müllerian hormone (AMH) level associated with body weight and metabolic, and hormonal disturbances in women with and without polycystic ovary syndrome? Eur J Obstet Gynecol Reprod Biol. 2011;158(2):254–9.
    1. Halawaty S, ElKattan E, Azab H, ElGhamry N, Al-Inany H. Effect of obesity on parameters of ovarian reserve in premenopausal women. J Obstet Gynecol Canada: JOGC = Journal d’obstetrique et gynecologie du Can : JOGC. 2010;32(7):687–90.
    1. Overbeek A, Broekmans FJ, Hehenkamp WJ, Wijdeveld ME, van Disseldorp J, van Dulmen-den Broeder E, et al. Intra-cycle fluctuations of anti-Müllerian hormone in normal women with a regular cycle: a re-analysis. Reprod Biomed Online. 2012;24(6):664–9.
    1. Simoes-Pereira J, Nunes J, Aguiar A, Sousa S, Rodrigues C, Sampaio Matias J, et al. Influence of body mass index in anti-Mullerian hormone levels in 951 non-polycystic ovarian syndrome women followed at a reproductive medicine unit. Endocrine. 2018;61(1):144–8.
    1. Reinehr T, Kulle A, Rothermel J, Knop C, Lass N, Bosse C, et al. Weight loss in obese girls with polycystic ovarian syndrome is associated with a decrease in Anti-Muellerian Hormone concentrations. Clin Endocrinol (Oxf) 2017;87(2):185–93.
    1. Foroozanfard F, Rafiei H, Samimi M, Gilasi HR, Gorjizadeh R, Heidar Z, et al. The effects of dietary approaches to stop hypertension diet on weight loss, anti-Müllerian hormone and metabolic profiles in women with polycystic ovary syndrome: A randomized clinical trial. Clin Endocrinol (Oxf) 2017;87(1):51–8.
    1. Nybacka Å, Carlström K, Fabri F, Hellström PM, Hirschberg AL. Serum antimüllerian hormone in response to dietary management and/or physical exercise in overweight/obese women with polycystic ovary syndrome: secondary analysis of a randomized controlled trial. Fertil Steril. 2013;100(4):1096–102.
    1. Thomson RL, Buckley JD, Moran LJ, Noakes M, Clifton PM, Norman RJ, et al. The effect of weight loss on anti-Müllerian hormone levels in overweight and obese women with polycystic ovary syndrome and reproductive impairment. Hum Reprod (Oxford England) 2009;24(8):1976–81.
    1. Moini A, Arabipoor A, Hemat M, Ahmadi J, Salman-Yazdi R, Zolfaghari Z. The effect of weight loss program on serum anti-Müllerian hormone level in obese and overweight infertile women with polycystic ovary syndrome. Gynecol Endocrinol. 2019;35(2):119–23.
    1. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84(10):3666–72.
    1. Fraissinet A, Robin G, Pigny P, Lefebvre T, Catteau-Jonard S, Dewailly D. Use of the serum anti-Mullerian hormone assay as a surrogate for polycystic ovarian morphology: impact on diagnosis and phenotypic classification of polycystic ovary syndrome. Hum Reprod. 2017;32(8):1716–22.
    1. Pigny P, Merlen E, Robert Y, Cortet-Rudelli C, Decanter C, Jonard S, et al. Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J Clin Endocrinol Metab. 2003;88(12):5957–62.
    1. Dewailly D, Robin G, Peigne M, Decanter C, Pigny P, Catteau-Jonard S. Interactions between androgens, FSH, anti-Mullerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary. Hum Reprod Update. 2016;22(6):709–24.
    1. Laven JS, Mulders AG, Visser JA, Themmen AP, De Jong FH, Fauser BC. Anti-Mullerian hormone serum concentrations in normoovulatory and anovulatory women of reproductive age. J Clin Endocrinol Metab. 2004;89(1):318–23.
    1. Dietz de Loos A, Hund M, Buck K, Meun C, Sillman J, Laven JSE. Antimüllerian hormone to determine polycystic ovarian morphology. Fertil Steril. 2021;116(4):1149–57.
    1. Stener-Victorin E, Holm G, Labrie F, Nilsson L, Janson PO, Ohlsson C. Are there any sensitive and specific sex steroid markers for polycystic ovary syndrome? J Clin Endocrinol Metab. 2010;95(2):810–9.
    1. Lim SS, Norman RJ, Davies MJ, Moran LJ. The effect of obesity on polycystic ovary syndrome: a systematic review and meta-analysis. Obes reviews: official J Int Association Study Obes. 2013;14(2):95–109.
    1. Moran LJ, Pasquali R, Teede HJ, Hoeger KM, Norman RJ. Treatment of obesity in polycystic ovary syndrome: a position statement of the Androgen Excess and Polycystic Ovary Syndrome Society. Fertil Steril. 2009;92(6):1966–82.
    1. Piltonen T, Morin-Papunen L, Koivunen R, Perheentupa A, Ruokonen A, Tapanainen JS. Serum anti-Müllerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovary syndrome. Hum Reprod (Oxford England) 2005;20(7):1820–6.
    1. Huber-Buchholz M-M, Carey DGP, Norman RJ. Restoration of Reproductive Potential by Lifestyle Modification in Obese Polycystic Ovary Syndrome: Role of Insulin Sensitivity and Luteinizing Hormone1. J Clin Endocrinol Metabolism. 1999;84(4):1470–4.
    1. Chiofalo F, Ciuoli C, Formichi C, Selmi F, Forleo R, Neri O, et al. Bariatric Surgery Reduces Serum Anti-mullerian Hormone Levels in Obese Women With and Without Polycystic Ovarian Syndrome. Obes Surg. 2017;27(7):1750–4.
    1. Dalle Grave R, Calugi S, Molinari E, Petroni ML, Bondi M, Compare A, et al. Weight loss expectations in obese patients and treatment attrition: an observational multicenter study. Obes Res. 2005;13(11):1961–9.
    1. Inelmen EM, Toffanello ED, Enzi G, Gasparini G, Miotto F, Sergi G, et al Predictors of drop-out in overweight and obese outpatients. International journal of obesity (2005). 2005;29(1):122-8.

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