In recent years, the effects of androgens on metabolic and body weight regulation systems and their underlying mechanisms have been gradually revealed in females. In women and experimental animals of reproductive age, androgen excess can adversely affect metabolic functioning, appetite, and body weight regulation. In addition, excess androgens can increase the risk of metabolic disorders, such as obesity, insulin resistance, and diabetes. These unfavorable effects of androgens are induced by alterations in the actions of hypothalamic appetite-regulatory factors, reductions in energy expenditure, insulin resistance in skeletal muscle, and β-cell dysfunction. Interestingly, these unfavorable effects of androgens on metabolic and body-weight regulation systems are neither observed nor evident in ovariectomized animals and post-menopausal women, indicating that the adverse effects of androgens might be dependent on the estrogen milieu. Recent findings may provide novel sex- and age-specific strategies for treating metabolic diseases.

Polycystic ovary syndrome (PCOS) is frequently seen in females of reproductive age and is associated with metabolic disorders that are exacerbated by obesity. Although body weight reduction programs via diet and lifestyle changes are recommended for modifying reproductive and metabolic phenotypes, the drop-out rate is high. Thus, an efficacious, safe, and continuable treatment method is needed. Recent studies have shown that oxytocin (OT) reduces body weight gain and food intake, and promotes lipolysis in some mammals, including humans (especially obese individuals), without any adverse effects. In the present study, we evaluated the changes in endogenous OT levels, and the effects of acute and chronic OT administration on body weight changes, food intake, and fat mass using novel dihydrotestosterone-induced PCOS model rats. We found that the serum OT level was lower in PCOS model rats than in control rats, whereas the hypothalamic OT mRNA expression level did not differ between them. Acute intraperitoneal administration of OT during the dark phase reduced the body weight gain and food intake in PCOS model rats, but these effects were not observed in control rats. In contrast, chronic administration of OT decreased the food intake in both the PCOS model rats and control rats. These findings indicate that OT may be a candidate medicine that is efficacious, safe, and continuable for treating obese PCOS patients.

Oxytocin (OT) affects many behavioral, psychological, and physiological functions, including appetite and body weight regulation. Central and peripheral OT levels are markedly affected by gonadal steroids, especially estrogen, and the anorectic effects of estrogen are partially mediated by OT in rodents. In this study, the relationship between the estrogen milieu and serum OT levels was evaluated in women of reproductive age under physiological (n = 9) and supraphysiological estrogenic conditions (n = 7). Consequently, it was found that serum OT levels were increased in physiological (the ovulatory phase) and supraphysiological (on the day of the human chorionic gonadotropin trigger in an ovarian stimulation cycle) estrogenic conditions, and that serum OT levels were positively correlated with serum estradiol levels. On the other hand, serum OT levels were negatively correlated with serum progesterone levels, and there was no correlation between serum and follicular OT levels. These results suggest that OT levels may be positively and negatively regulated by estrogen and progesterone, respectively, in humans. However, the physiological roles of these actions of gonadal steroids on OT remain unclear.

Aim: To establish cut‐off values for anti‐Müllerian hormone (AMH) and antral follicle count (AFC) in the diagnostic criteria for polycystic ovary syndrome (PCOS) applicable to the Japan Society of Obstetrics and Gynecology (JSOG) 2024 criteria and the Rotterdam/International Evidence‐Based Guideline for the assessment and management of PCOS (IEBG) 2023 criteria based on a nationwide survey, respectively, taking into account age, assays, and structure of the diagnostic criteria.Methods: Data were collected for 986 PCOS cases and 965 control cases using a national survey in Japan and used to establish cut‐off values for AMH and AFC.Results: Serum AMH levels were significantly higher in the PCOS group compared to the control group. Serum AMH showed a significant negative correlation with age and significant positive correlation with AFC in both groups. In multiple regression analysis, serum AMH level was independently affected by AFC and total testosterone. AMH cut‐off values suitable for the JSOG 2024 criteria and the Rotterdam/IEBG 2023 criteria were separately established for the 20–29 and 30–39 years of age groups, respectively, and for Access, Lumipulse and Elecsys/ECLusys, respectively. AFC cut‐off values suitable for the JSOG 2024 criteria and Rotterdam/IEBG 2023 criteria were also established separately. AFC exhibited statistically greater variability than AMH.Conclusion: The serum AMH level is the biochemical representation of ovarian findings in PCOS and considered objective and highly reliable. Therefore, it could serve as a surrogate for AFC as a marker of polycystic ovarian morphology in diagnostic criteria.

Aim: Describe the current phenotypes and clinical laboratory data regarding polycystic ovary syndrome (PCOS) in Japan, taking into account ethnic differences and obesity status.Methods: Data for 986 PCOS cases and 965 control cases were collected using a nationwide survey in Japan. Obese/overweight (body mass index [BMI] ≥25 kg/m²) and non‐obese/overweight (BMI <25 kg/m²) cases were compared.Results: Japanese PCOS cases predominantly involved non‐obese/overweight patients, accounting for 75% of all cases. Among non‐obese/overweight PCOS cases, the incidence of both amenorrhea and clinical/biochemical hyperandrogenism was significantly lower than in obese/overweight PCOS cases, whereas the rate of elevated serum luteinizing hormone (LH) level was significantly higher. Even though the incidence of hirsutism in Japan is only 13.5%, the detection rate for hyperandrogenism increased by as much as 30.4% when hirsutism was added to the Japan Society of Obstetrics and Gynecology (JSOG) criteria for the diagnosis of hyperandrogenism in addition to elevated serum total testosterone level. When evaluated based on timing of blood sampling, the LH level and LH/follicle‐stimulating hormone ratio determined at the initial consultation involving a chief complaint of irregular menstrual cycle (after confirming the absence of follicles measuring ≥1 cm in diameter) were significantly higher than on days 2–3 or 4–6 of the menstrual cycle.Conclusions: Ethnic differences, including obesity status, affected the phenotype and clinical laboratory data of Japanese PCOS patients, such as the incidence rates of clinical/biochemical hyperandrogenism and the rate of elevated basal LH level. Adding hirsutism to the JSOG 2024 criteria would enhance the accuracy of PCOS diagnosis and enhance consistency with the Rotterdam 2003 criteria. Measuring basal LH level is useful for assessing the endocrinologic characteristics of Japanese PCOS cases, as well as lean Asian PCOS cases, but the timing of blood sampling can affect the result.