{
    "abstract": "Is resumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity associated with differential changes in endocrine and metabolic parameters (weight, insulin resistance, anti-M\u00fcllerian hormone (AMH), and androgens) compared to women with PCOS who remained anovulatory?\nResumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity is associated with changes in serum 11\u03b2-hydroxyandrostenedione (11OHA4) concentrations.\nLifestyle interventions have been shown to reduce clinical and biochemical hyperandrogenism in women with PCOS. Weight loss of 5-10% may reverse anovulatory status, thereby increasing natural conception rates. However, the mechanisms underlying why some women with PCOS remain anovulatory and others resume ovulation after weight loss are unclear. Reproductive characteristics at baseline and a greater degree of change in endocrine and metabolic features with lifestyle intervention may be crucial for ovulatory response.\nWe used data and samples originating from an earlier randomized controlled trial (RCT), which examined the efficacy of a 6-month lifestyle intervention prior to infertility treatment compared to prompt infertility treatment on live birth rate in women with obesity. A total of 577 women with obesity (BMI > 29\u2009kg/m2) were randomized between 2009 and 2012. Anovulatory women with PCOS who were allocated to the intervention arm of the original RCT (n\u2009=\u200995) were included in the current analysis.\nWe defined women as having resumed ovulation (RO+) based on the following criteria: spontaneous pregnancy; or assignment to expectant management; or IUI in natural cycles as the treatment strategy after lifestyle intervention. Steroid hormones were measured using liquid chromatography tandem mass spectrometry. Generalized estimating equations with adjustment for baseline measures and interaction between group and time was used to examine differences in changes of endocrine and metabolic parameters between RO+ (n\u2009=\u200934) and persistently anovulatory women (RO-, n\u2009=\u200961) at 3 and 6\u2009months after intervention.\nAt baseline, the mean\u2009\u00b1\u2009SD age was 27.5\u2009\u00b1\u20093.6\u2009years in the RO+ group and 27.9\u2009\u00b1\u20094.1\u2009years in the RO- group (P\u2009=\u20090.65), and the mean\u2009\u00b1\u2009SD weights were 101.2\u2009\u00b1\u20099.5\u2009kg and 105.0\u2009\u00b1\u200914.6\u2009kg, respectively (P\u2009=\u20090.13). Baseline AMH concentrations showed significant differences between RO+ and RO- women (median and interquartile range [IQR] 4.7 [3.2; 8.3] versus 7.2 [5.3; 10.8] ng/ml, respectively). Baseline androgen concentrations did not differ between the two groups. During and after lifestyle intervention, both groups showed weight loss; changes in 11OHA4 were significantly different between the RO+ and RO groups (P-value for interaction\u2009=\u20090.03). There was a similar trend for SHBG (interaction P-value\u2009=\u20090.07), and DHEA-S (interaction P-value\u2009=\u20090.06), with the most pronounced differences observed in the first 3\u2009months. Other parameters, such as AMH and FAI, decreased over time but with no difference between the groups.\nNo high-resolution transvaginal ultrasonography was used to confirm ovulatory status at the end of the lifestyle program. The small sample size may limit the robustness of the results.\nReduction of androgen concentrations during and after lifestyle intervention is associated with recovery of ovulatory cycles. If our results are confirmed in other studies, androgen concentrations could be monitored during lifestyle intervention to provide individualized recommendations on the timing of resumption of ovulation in anovulatory women with PCOS and obesity.\nThe study was supported by a grant from ZonMw, the Dutch Organization for Health Research and Development (50-50110-96-518). The Department of Obstetrics and Gynecology of the UMCG received an unrestricted educational grant from Ferring Pharmaceuticals BV, The Netherlands. A.H. reports consultancy for the development and implementation of a lifestyle App MyFertiCoach developed by Ferring Pharmaceutical Company. All other authors have no conflicts to declare.\nThe LIFEstyle RCT was registered at the Dutch trial registry (NTR 1530).",
    "authors": [
        {
            "affiliation": "Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.",
            "firstname": "Z",
            "initials": "Z",
            "lastname": "Wang"
        },
        {
            "affiliation": "Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.",
            "firstname": "M",
            "initials": "M",
            "lastname": "Van Faassen"
        },
        {
            "affiliation": "Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.",
            "firstname": "H",
            "initials": "H",
            "lastname": "Groen"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.",
            "firstname": "A E P",
            "initials": "AEP",
            "lastname": "Cantineau"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.",
            "firstname": "A",
            "initials": "A",
            "lastname": "Van Oers"
        },
        {
            "affiliation": "Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.",
            "firstname": "A",
            "initials": "A",
            "lastname": "Van der Veen"
        },
        {
            "affiliation": "Department of Clinical Biochemistry, Wythenshawe Hospital, Manchester NHS Foundation Trust, Manchester, UK.",
            "firstname": "J M",
            "initials": "JM",
            "lastname": "Hawley"
        },
        {
            "affiliation": "Department of Clinical Biochemistry, Wythenshawe Hospital, Manchester NHS Foundation Trust, Manchester, UK.",
            "firstname": "B G",
            "initials": "BG",
            "lastname": "Keevil"
        },
        {
            "affiliation": "Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.",
            "firstname": "I P",
            "initials": "IP",
            "lastname": "Kema"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.",
            "firstname": "A",
            "initials": "A",
            "lastname": "Hoek"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.",
    "doi": "10.1093/humrep/deae058",
    "journal": "Human reproduction (Oxford, England)",
    "keywords": [
        "11\u03b2-hydroxyandrostenedione",
        "PCOS",
        "androgens",
        "anti-M\u00fcllerian hormone",
        "lifestyle intervention",
        "obesity",
        "resumption of ovulation"
    ],
    "methods": null,
    "publication_date": "2024-03-20",
    "pubmed_id": "38503490\n29024702\n16940456\n20036327\n24821925\n28378209\n23065822\n26691645\n16189250\n8150098\n31926069\n27799625\n31295971\n24823705\n21771766\n24026057\n25846979\n22767467\n30921477\n3899825\n32770239\n17652213\n27192672\n20579357\n15140873\n23876536\n27901631\n16827825\n2026121\n14688154\n16199429\n30033227\n19380385\n32797203\n14678951\n29324776\n30922617\n27798042\n31525346",
    "results": null,
    "title": "Resumption of ovulation in anovulatory women with PCOS and obesity is associated with reduction of 11\u03b2-hydroxyandrostenedione concentrations.",
    "xml": "<Element 'PubmedArticle' at 0x788503d728e0>"
}