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Rachel Forfar Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, UK

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Mashal Hussain Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK

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Puneet Khurana Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, UK

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Jennifer Cook Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, UK

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Steve Lewis Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, UK

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Dillon Popat Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK

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David Jackson Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK

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Ed McIver Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, UK

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Jeff Jerman Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, UK

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Debra Taylor Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, UK

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Adrian JL Clark Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK

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Li F Chan Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK

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The overproduction of adrenocorticotropic hormone (ACTH), in conditions such as Cushing’s disease and congenital adrenal hyperplasia (CAH), leads to significant morbidity. Current treatment with glucocorticoids does not adequately suppress plasma ACTH, resulting in excess adrenal androgen production. At present, there is no effective medical treatment in clinical use that would directly block the action of ACTH. Such a therapy would be of great clinical value. ACTH acts via a highly selective receptor, the melanocortin-2 receptor (MC2R) associated with its accessory protein MRAP. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and the high degree of ligand specificity suggest that antagonism of this receptor could provide a useful therapeutic strategy in the treatment of conditions of ACTH excess. To this end, we screened an extensive library of low-molecular-weight drug-like compounds for MC2R antagonist activity using a high-throughput homogeneous time-resolved fluorescence cAMP assay in Chinese hamster ovary cells stably co-expressing human MC2R and MRAP. Hits that demonstrated MC2R antagonist properties were counter-screened against the β2 adrenergic receptor and dose–response analysis undertaken. This led to the identification of a highly specific MC2R antagonist capable of antagonising ACTH-induced progesterone release in murine Y-1 adrenal cells and having selectivity for MC2R amongst the human melanocortin receptors. This work provides a foundation for the clinical investigation of small-molecule ACTH antagonists as therapeutic agents and proof of concept for the screening and discovery of such compounds.

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Meghnaa Hebbar College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

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Halimah Khalil College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

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Nawal Zia College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

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Jameela Sheikh College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

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Eka Melson University of Leicester, Leicester, United Kingdom

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Meri Davitadze Clinic NeoLab, Tbilisi, Georgia

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Helena Gleeson Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom

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Tejal Lathia Apollo Hospitals, Mumbai, India

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Chitra Selvan Department of Endocrinology, M S Ramaiah Medical College, Bengaluru, India

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Punith Kempegowda Clinic NeoLab, Tbilisi, Georgia
Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom

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PCOS SEva Working Group
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PCOS SEva Working Group

With increasing evidence of emotional well-being disorders associated with polycystic ovary syndrome (PCOS), effective screening processes are of utmost importance. We studied the impact of using questionnaires to screen for emotional and psychosexual well-being across different models of care for PCOS. We analysed the data from the surveys to assess the difference in the prevalence of emotional and psychosexual ill-being across ethnicity and region. In this prospective cohort study, we invited all women attending consultations for PCOS in Birmingham, UK, and Bengaluru and Navi Mumbai, India. Those who consented to participate in the study were invited to complete a pre-clinic survey about socio-demographic data, Hospital Anxiety and Depression Scale (HADS), Body Image Concern Inventory (BICI), Beliefs about Obese Person scale (BAOP), and Female Sexual Function Index score (FSFI) and a post-clinic survey on clinic experience, lifestyle advice, and specialist referral. A total of 115 women were included in this study. The rate of questionnaire completion was 98.3% (113/115), 97.4% (112/115), 93.04% (107/115), and 84.3% (97/115) for HADS, BICI, BAOP, and FSFI, respectively. In the post-clinic survey, 28.8% reported they were screened for anxiety, 27.1% for depression, and 45.8% for body image concerns. The prevalence of anxiety, depression, and body dysmorphic disorder through pre-clinic survey was 56.5% (50.0% UK vs 59.5% India, P = 0.483), 16.5% (13.9% UK vs 17.7% India, P = 0.529), and 29.6% (36.1% UK vs 26.6% India, P = 0.208), respectively. Surveys with validated questionnaires can improve screening for emotional and psychosexual well-being associated with PCOS which may be missed by ad hoc screening during consultations.

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Xiying Zeng The Third Clinical Medical College, Fujian Medical University, Fuzhou, China

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Yinxiang Huang Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, China

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Mulin Zhang Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, China

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Yun Chen The Third Clinical Medical College, Fujian Medical University, Fuzhou, China

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Jiawen Ye The Third Clinical Medical College, Fujian Medical University, Fuzhou, China

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Yan Han School of Medicine, Xiamen University, Xiamen, China

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Danyan Ma School of Medicine, Xiamen University, Xiamen, China

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Xin Zheng Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, China

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Xiaohong Yan Reproductive Medicine Center, The First Affiliated Hospital of Xiamen University, Xiamen, China

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Changqin Liu The Third Clinical Medical College, Fujian Medical University, Fuzhou, China
Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, China
Fujian Province Key Laboratory of Diabetes Translational Medicine, Xiamen, China

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Objective

Anti-Müllerian hormone (AMH) is recognized as the most important biomarker for ovarian reserve. In this cross-sectional study, we aimed to explore the potential association of AMH with central obesity or general obesity in women with polycystic ovary syndrome (PCOS).

Methods

In this cross-sectional study, 179 patients with PCOS were enrolled and underwent anthropometric measurements (BMI and waist circumference (WC)) and serum AMH level detection. Pearson’s correlation and multivariable logistic regression analyses were performed to determine the associations of AMH with central obesity and general obesity.

Results

Subjects with increasing BMI showed significantly lower values of AMH (median (interquartile range (IQR)) 8.95 (6.03–13.60) ng/mL in normal weight group, 6.57 (4.18–8.77) ng/mL in overweight group, and 6.03 (4.34–9.44) ng/mL in obesity group, P = 0.001), but higher levels of systolic blood pressure, fasting insulin, total cholesterol, triglycerides, LDL-c, obesity indices (WC, hip circumferences, waist-to-hip ratio, waist-to-height ratio (WHtR), and Chinese visceral adiposity index (CVAI)). Compared with the group of PCOS women without central obesity, the group with central obesity had significantly lower value of AMH (median (IQR) 8.56 (5.29–12.96) ng/mL vs 6.22 (4.33–8.82) ng/mL; P = 0.003). Pearson’s correlation analysis showed that AMH was significantly and negatively correlated with BMI (r = −0.280; P < 0.001), WC (r = −0.263; P < 0.001), WHtR (r = −0.273; P < 0.001), and CVAI (r = −0.211; P = 0.006). Multivariate logistic regression analysis with adjustment for potential confounding factors showed that AMH was independently and negatively associated with central obesity but was not significantly associated with general obesity.

Conclusions

AMH was independently and negatively associated with central obesity. Closely monitoring the WC and AMH should be addressed in terms of assessing ovarian reserve in women with PCOS.

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Jie Yang J Yang, Reproductive Medicine Center, Shunde Hospital of Southern Medical University, Foshan, China

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Min Lin M Lin, Reproductive Medicine Center, The First People's Hospital of Yulin, Yulin, China

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Xiaoyan Tian X Tian, Reproductive Medicine Center, Shunde Hospital of Southern Medical University, Foshan, China

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Chujun Li C Li, Reproductive Medicine Center, Shunde Hospital of Southern Medical University, Foshan, China

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Haocun Wu H Wu, Department of Clinical Laboratory, Shunde Hospital of Southern Medical University, Foshan, China

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Ling Deng L Deng, Reproductive Medicine Center, Shunde Hospital of Southern Medical University, Foshan, China

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Xuelan Li X Li, Reproductive Medicine Center, Shunde Hospital of Southern Medical University, Foshan, China

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Xin Chen X Chen, Reproductive Medicine Center, Shunde Hospital of Southern Medical University, Foshan, China

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Purpose: Our study aimed to assess the relationship between serum adipokines and insulin resistance (IR) in women with polycystic ovary syndrome (PCOS), as well as explore the predictive value of adipokines on IR in PCOS.

Methods: This was a prospective cross-sectional study. 154 women with PCOS were included from July 2021 to September 2022 who underwent gonadal steroid hormone measurement, lipid profile, oral glucose tolerance test and homeostasis model assessment (HOMA)-IR. Adiponectin (APN), leptin and secreted frizzled-related protein (Sfrp5) were measured by immunoturbidimetry and enzyme-linked immunosorbent assay. Women with PCOS were categorised based on the presence of IR.

Results: Women with PCOS with IR (n=99) had significantly lower APN level and APN to leptin ratio (A/L ratio) than those without IR (n=55), whereas serum levels of leptin and Sfrp5 were similar between the two groups. In multivariable linear regression analysis, serum log (APN) and log (A/L ratio) were associated with log(HOMA-IR), the association was statistically significant after adjusting for body mass index (BMI) and free androgen index. The area under the ROC curve (95% CI) for APN and A/L ratio were 0.726 (0.644–0.807; P<0.001) and 0.660(0.569–0.751; P<0.01), with cutoff values of 5.225 mg/L (Youden index ¼ 0.364) and 1.438 (Youden index ¼ 0.265) respectively.

Conclusion: Our study demonstrated that serum APN was negatively related to IR. Serum APN may be useful as a clinical marker for IR in women with PCOS. Our findings warrant further investigations into the function of APN in the pathogenesis of IR in women with PCOS.

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Srdjan Pandurevic Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Ilaria Mancini Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
Unit of Gynecology and Obstetrics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy

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Dimitri Mitselman Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Matteo Magagnoli Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Rita Teglia Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Roberta Fazzeri Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Paola Dionese Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Carolina Cecchetti Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Massimiliamo Caprio Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, Rome, Italy
Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele, Rome, Italy

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Costanzo Moretti Department of Systems Medicine, Unit of Endocrinology, University of Rome Tor Vergata, Rome, Italy

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Justyna Sicinska Dermatology Clinic of CSK MSWiA Hospital, Warsaw, Poland

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Alessandro Agostini Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna, Italy

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Domenica Gazineo Teaching Hospital, S. Orsola Hospital, Bologna, Italy

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Lea Godino Teaching Hospital, S. Orsola Hospital, Bologna, Italy

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Ignacio Sajoux Epigenomics in Endocrinology and Nutrition Group, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Spain
Medical Department Pronokal Group, Barcelona, Spain

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Flaminia Fanelli Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Cristina M Meriggiola Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
Unit of Gynecology and Obstetrics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy

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Uberto Pagotto Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Alessandra Gambineri Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Objective

The aim of this study isto assess the efficacy of a very low-calorie ketogenic diet (VLCKD) method vs a Mediterranean low-calorie diet (LCD) in obese polycystic ovary syndrome (PCOS) women of a reproductive age.

Design

Randomized controlled open-label trial was performed in this study. The treatment period was 16 weeks; VLCKD for 8 weeks then LCD for 8 weeks, according to the Pronokal® method (experimental group; n = 15) vs Mediterranean LCD for 16 weeks (control group; n = 15). Ovulation monitoring was carried out at baseline and after 16 weeks, while a clinical exam, bioelectrical impedance analysis (BIA), anthropometry, and biochemical analyses were performed at baseline, at week 8, and at week 16.

Results

BMI decreased significantly in both groups and to a major extent in the experimental group (−13.7% vs −5.1%, P = 0.0003). Significant differences between the experimental and the control groups were also observed in the reduction of waist circumference (−11.4% vs −2.9%), BIA-measured body fat (−24.0% vs −8.1%), and free testosterone (−30.4% vs −12.6%) after 16 weeks (P = 0.0008, P = 0.0176, and P = 0.0009, respectively). Homeostatic model assessment for insulin resistance significantly decreased only in the experimental group (P = 0.0238) but without significant differences with respect to the control group (−23% vs −13.2%, P > 0.05). At baseline, 38.5% of participants in the experimental group and 14.3% of participants in the control group had ovulation, which increased to 84.6% (P = 0.031) and 35.7% (P > 0.05) at the end of the study, respectively.

Conclusion

In obese PCOS patients, 16 weeks of VLCKD protocol with the Pronokal® method was more effective than Mediterranean LCD in reducing total and visceral fat, and in ameliorating hyperandrogenism and ovulatory dysfunction.

Significance statements

To the best of our knowledge, this is the first randomized controlled trial on the use of the VLCKD method in obese PCOS. It demonstrates the superiority of VLCKD with respect to Mediterranean LCD in reducing BMI with an almost selective reduction of fat mass and a unique effect of VLCKD in reducing visceral adiposity, insulin resistance, and in increasing SHBG with a consequent reduction of free testosterone. Interestingly, this study also demonstrates the superiority of the VLCKD protocol in improving ovulation, whose occurrence increased by 46.1% in the group treated by the VLCKD method against a rise of 21.4% in the group treated by Mediterranean LCD. This study extends the therapeutic approach possibilities in obese PCOS women.

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Panagiotis Anagnostis Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Irene Lambrinoudaki 2nd Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Medical School, Athens, Greece

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John C Stevenson National Heart and Lung Institute, Imperial College London, Royal Brompton and Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

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Dimitrios G Goulis Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Cardiovascular disease (CVD) is of major concern in women entering menopause. The changing hormonal milieu predisposes them to increased CVD risk, due to a constellation of risk factors, such as visceral obesity, atherogenic dyslipidemia, dysregulation in glucose homeostasis, non-alcoholic fatty liver disease and arterial hypertension. However, an independent association of menopause per se with increased risk of CVD events has only been proven for early menopause (<45 years). Menopausal hormone therapy (MHT) ameliorates most of the CVD risk factors mentioned above. Transdermal estrogens are the preferable regimen, since they do not increase triglyceride concentrations and they are not associated with increased risk of venous thromboembolic events (VTE). Although administration of MHT should be considered on an individual basis, MHT may reduce CVD morbidity and mortality, if commenced during the early postmenopausal period (<60 years or within ten years since the last menstrual period). In women with premature ovarian insufficiency (POI), MHT should be administered at least until the average age of menopause (50–52 years). MHT is contraindicated in women with a history of VTE and is not currently recommended for the sole purpose of CVD prevention. The risk of breast cancer associated with MHT is generally low and is mainly conferred by the progestogen. Micronized progesterone and dydrogesterone are associated with lower risk compared to other progestogens.

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Henryk F Urbanski Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon, USA
Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon, USA
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA
Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, Oregon, USA

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Kevin Mueller Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon, USA

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Cynthia L Bethea Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon, USA
Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon, USA
Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon, USA

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Like women, old female rhesus macaques undergo menopause and show many of the same age-associated changes, including perturbed activity/rest cycles and altered circulating levels of many hormones. Previous studies showed that administration of an estrogen agonist increased activity in female monkeys, that hormone therapy (HT) increased activity in postmenopausal women and that obesity decreased activity in women. The present study sought to determine if postmenopausal activity and circulating hormone levels also respond to HT when monkeys are fed a high-fat, high-sugar Western style diet (WSD). Old female rhesus macaques were ovo-hysterectomized (OvH) to induce surgical menopause and fed a WSD for 2 years. Half of the animals received estradiol-17β (E), beginning immediately after OvH, while the other half received placebo. Animals in both groups showed an increase in body weight and a decrease in overall activity levels. These changes were associated with a rise in both daytime and nocturnal serum leptin concentrations, but there was no change in serum concentrations of either cortisol or dehydroepiandrosterone sulfate (DHEAS). These data suggest that 2 years of HT has little or no effect on locomotor activity or circadian hormone patterns in menopausal macaques fed an obesogenic diet.

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Alan D Rogol Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA

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The overall incidence of sex chromosome aneuploidies is approximately 1 per 500 live-born infants, but far more common at conception. I shall review the fertility aspects of the sex chromosome trisomies, XXY, XYY, and XXX, with special reference to the karyotype 45,X/47,XXX. Each has a ‘specific’ (but variable) phenotype but may be modified by mosaicism. Although the alterations in the hypothalamic–pituitary–gonadal axis are important (and discussed), the emphasis here is on potential fertility and if one might predict that at various epochs within an individual’s life span: fetal, ‘mini’-puberty, childhood, puberty, and adulthood. The reproductive axis is often affected in females with the 47,XXX karyotype with diminished ovarian reserve and accelerated loss of ovarian function. Fewer than 5% of females with Turner syndrome have the 45,X/47,XXX karyotype. They have taller stature and less severe fertility issues compared to females with the 45,X or other forms of Turner syndrome mosaicism. For the 47,XXY karyotype, non-obstructive azoospermia is almost universal with sperm retrieval by micro-testicular sperm extraction possible in slightly fewer than half of the men. Men with the 47,XYY karyotype have normal to large testes and much less testicular dysfunction than those with the 47,XXY karyotype. They do have a slight increase in infertility compared to the reference population but not nearly as severe as those with the 47,XXY karyotype. Assisted reproductive technology, especially micro-testicular sperm extraction, has an important role, especially for those with 47,XXY; however, more recent data show promising techniques for the in vitro maturation of spermatogonial stem cells and 3D organoids in culture. Assisted reproductive technology is more complex for the female, but vitrification of oocytes has shown promising advances.

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D Santi Unit of Endocrinology, Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Unit of Endocrinology, Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy

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A R M Granata Unit of Endocrinology, Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy

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M Simoni Unit of Endocrinology, Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Unit of Endocrinology, Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy

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Introduction

The aim of this study is to comprehensively evaluate whether FSH administration to the male partner of infertile couples improves pregnancy rate, spontaneously and/or after assisted reproductive techniques (ART).

Methods

Meta-analysis of controlled clinical trials in which FSH was administered for male idiopathic infertility, compared with placebo or no treatment. Randomization was not considered as an inclusion criterion.

Results

We found 15 controlled clinical studies (614 men treated with FSH and 661 treated with placebo or untreated). Concerning the type of FSH, eight studies used recombinant FSH, whereas seven studies used purified FSH. Nine studies evaluated spontaneous pregnancy rate, resulting in an overall odds ratio (OR) of about 4.5 (CI: 2.17–9.33). Eight studies evaluated pregnancy rate after ART, showing a significant OR of 1.60 (CI: 1.08–2.37). Sub-dividing studies according to the FSH preparations (purified/recombinant), pregnancy rate improvement remained significant for each preparation. Eleven studies considered sperm quality after FSH treatment, finding a significant improvement of sperm concentration (2.66×106/ml, CI: 0.47–4.84), but not of concentration of sperm with progressive motility (1.22×106/ml, CI: −0.07 to 2.52). Three trials evaluated testicular volume, showing a non-significant increase in men treated (1.35 ml, CI: −0.44 to 3.14).

Conclusion

The results of controlled clinical trials available in the literature indicate an improvement of pregnancy rate after FSH administration to the male partner of infertile couples, both spontaneously and after ART. However, the heterogeneity of studies, the high risk of bias and the lack of precise criteria to guide FSH administration limit the strength of these results. Future studies should be designed to identify the markers of FSH response which are helpful in the decision-making process. Meanwhile, the use of FSH in the treatment of male infertility should be cautious.

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Pravik Solanki Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia
Alfred Health, Melbourne, Victoria, Australia

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Beng Eu Prahran Market Clinic, Victoria, Australia
Department of General Practice, Melbourne Medical School, The University of Melbourne, Victoria, Australia

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Jeremy Smith Faculty of Science, University of Western Australia, Perth, Australia

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Carolyn Allan Hudson Institute of Medical Research, Melbourne, Victoria, Australia

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Kevin Lee Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia

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Hypogonadism can result following anabolic steroid abuse. The duration and degree of recovery from anabolic steroid-induced hypogonadism (ASIH) is immensely variable, and there is a paucity of prospective controlled data characterising the trajectory of natural recovery following cessation. This poses difficulties for users trying to stop androgen abuse, and clinicians wanting to assist them. The objective of this paper was to synthesise evidence on the physical, psychological and biochemical patterns of ASIH recovery. We present the pathophysiology of ASIH through a literature review of hypothalamic–pituitary–testosterone axis recovery in supraphysiological testosterone exposure. This is followed by a scoping review of relevant observational and interventional studies published on PubMed and finally, a conclusion that is an easy reference for clinicians helping patients that are recovering from AAS abuse. Results indicate that ASIH recovery depends on age and degree of androgen abuse, with physical changes like testicular atrophy expected to have near full recovery over months to years; spermatogenesis expected to achieve full recovery over months to years; libido returning to baseline over several months (typically less potent than during AAS use); and recovery from gynaecomastia being unlikely. For psychological recovery, data are insufficient and conflicting, indicating a transient withdrawal period which may be followed by persisting longer-term milder symptoms. For biochemical recovery, near complete recovery of testosterone is seen over months, and complete gonadotropin recovery is expected over 3–6 months. Further prospective studies are indicated to more closely describe patterns of recovery.

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