Postmenopausal hyperandrogenism is a rare yet clinically relevant condition. It can result from a wide variety of sources and etiologies, from benign functional disorders to life-threatening androgen-secreting tumors. Polycystic ovary syndrome is the most frequent cause of hyperandrogenism in postmenopausal patients. Ovarian or adrenal tumors are rare but must be promptly recognized because any delay in diagnosis is associated with a significant risk of mortality. Sudden onset and rapid progression of symptoms or virilizing features are clinical red flags that must lead to the use of imaging to rule out malignancy. Hormonal assessment using accurate assays, in combination with targeted imaging, dynamic testing in selected cases, and a structured diagnostic algorithm will help to establish the etiology of androgen excess in less severe cases. Surgery is the cornerstone of treatment in most cases of severe hyperandrogenism. Gonadotropin-releasing hormone analogs or low-dose glucocorticoids may be helpful for the control of symptoms in gonadal or adrenal functional hyperandrogenism, respectively. Antiandrogens are also helpful in patients with mild functional hyperandrogenism who are concerned about dermocosmetic symptoms. In cases of endocrinopathies or iatrogenic causes, treatment of the underlying cause and avoidance of the drug responsible are needed. This review summarizes the varied etiology of postmenopausal androgen excess, and emphasizes the importance of an accurate diagnostic workup and tailored management.

46,XY disorders of sex development (DSDs) are rare congenital conditions resulting from impaired gonadal differentiation and/or steroidogenesis. The NR5A1 gene encodes steroidogenic factor 1 (SF-1), a key regulator of gonadal development and endocrine function, and pathogenic variants are associated with a broad phenotypic spectrum that may present beyond the neonatal period. We report the case of a 12-year-and-6-month-old phenotypic female adolescent presenting with severe hirsutism, acne, primary amenorrhea, and progressive virilization. Hormonal evaluation demonstrated hyperandrogenism with hypergonadotropic hypogonadism. Imaging revealed the absence of a normal uterus and ovaries, with the presence of a Müllerian remnant, along with bilateral gonadal structures consistent with testicular tissue, and cytogenetic analysis showed a 46,XY karyotype. Genetic testing identified a novel heterozygous pathogenic NR5A1 splice-site variant (c.871-2A>G), confirming the diagnosis of 46,XY DSD. Multidisciplinary management included bilateral gonadectomy followed by estrogen replacement therapy. This case highlights an uncommon adolescent presentation of 46,XY DSD revealed by severe hyperandrogenism in a phenotypic female individual and underscores the importance of molecular genetic testing for accurate diagnosis, management, and long-term follow-up.

Hyperandrogenism in women typically presents with hirsutism and other virilizing features. When it presents with accelerated clinical features and/or high androgen levels (total testosterone > 5 nmol/L) (>145 ng/dL) (reference range, <2.4 nmol/L [SI: <70 ng/dL]), particularly in the post-menopausal state, an underlying ovarian or adrenal neoplasm should be considered. With ovarian pathology, androgen-secreting ovarian tumors and ovarian hyperthecosis are the key differential diagnoses. The recommended treatment for androgen-secreting ovarian tumors (ASOTs) is surgical removal. In contrast, ovarian hyperthecosis may be managed conservatively, provided an androgen-secreting malignant tumor has been excluded. Clarifying this diagnostic uncertainty is a challenge, and imaging and biochemical tests are not always diagnostic. There is additionally a need for better medical treatment in patients with benign ASOTs. We report two cases of female hyperandrogenism with a radiologically identified ovarian lesion, managed with a gonadotropin-releasing hormone (GnRH) antagonist, namely, degarelix. Degarelix was helpful for both diagnosis and treatment of symptoms. We highlight its potential role in diagnosis and medical management, particularly as an option for patients who are unwilling or unable to undergo immediate surgery. We also hypothesize that a fall in total testosterone following GnRH antagonist injection may indicate that an ovarian tumor is benign.

This observational study was designed to establish and validate a stigma prediction model for patients with polycystic ovary syndrome (PCOS). The stigma risk scoring table for overweight and obese patients with PCOS has good predictive ability. When an overweight or obese patient with PCOS presents, the prediction model allows clinic staff to rapidly grade hirsutism, acne, and acanthosis, determine fertility desire, and quantify anxiety. Low-risk patients then receive standard care, whereas high-risk patients receive precision interventions. Unlike the traditional approach, this clinical prediction model incorporates not only laboratory values but also body-image concerns and psychological well-being, providing more comprehensive management for women with PCOS. To preliminarily explore the associations among stigma, PCOS signs, anxiety, and depression. A total of 124 overweight and obese patients with PCOS were selected using convenience sampling. The patients in the order of clinic visit time were divided into a modeling set and a validation set at a ratio of 3:1. Univariate analysis was first performed, normally distributed continuous variables were compared using t-tests, non-normally distributed continuous variables with nonparametric rank-sum tests, and categorical variables with χ2 tests. Independent risk factors for stigma were identified using multivariable logistic regression, and a nomogram was constructed. The model's discrimination and calibration were evaluated with the receiver operating characteristic curve and calibration curve. Internal validation was subsequently conducted on the validation data set to assess model performance comprehensively. Hirsutism (odds ratio [OR]=0.075, 95%Cl: 0.015-0.368) , acne (OR=0.210, 95%Cl: 0.050-0.878) , acanthosis nigricans (OR=0.184, 95%Cl: 0.044-0.073) , fertility requirements (OR=0.212, 95%Cl: 0.051-0.890) , and anxiety (OR=1.217, 95%Cl: 1.074-1.378) were independent influencing factors for stigma in these patients (P < .05). The constructed prediction model also demonstrated good predictive ability, with area under the curve values of 0.941 and 0.803 for the modeling and validation sets, respectively. Internal validation using 1000 bootstrap resamples revealed a mean area under the receiver operating characteristic curve area under the curve of 0.941.

5α-androstane-3α,17β-diol 17-glucuronide (3α-diol G) is a testosterone metabolite and an important biomarker of hormonal dysregulation, including polycystic ovary syndrome (PCOS) and virilizing syndromes in women such as idiopathic hirsutism. While immunoassay kits are commonly used for its quantification in clinical laboratories, these methods are prone to interference due to the structural similarity among steroidal compounds. In this study, we developed and validated a robust LC-MS/MS method for the quantification of 3α-diol G in human serum. Extraction was performed using a μelution SPE approach, allowing the achievement of a suitable LLOQ (0.140 ng/mL) with a low sample volume (100 μL). The chromatographic method successfully separated major known interferences, including glucuronidated androsterone (ADT-G) and etiocholanolone (Etio-G), and resolved unknown coeluting compounds that could otherwise lead to overestimation. Additionally, monitoring the transitions of the most common phospholipid showed no interference from these species. Method validation followed CLSI recommendations, assessing imprecision, accuracy, linearity, limit of quantification, carryover, and stability. The routine analysis incorporated a system suitability protocol based on ion ratio monitoring to detect potential coeluting interferences prior to batch analysis. This work highlights the importance of chromatographic separation and ion ratio monitoring in steroid analysis and provides a reliable alternative to immunoassay-based quantification of 3α-diol G.

Severe hyperandrogenism with new-onset virilization in postmenopausal women is rare and often associated with androgen-secreting tumors. Nevertheless, a comprehensive differential diagnosis must be considered, including ovarian hyperthecosis and Cushing syndrome. We report a 71-year-old woman with progressive hirsutism over 1-2 years, presenting with severe hyperandrogenism and insulin resistance. Physical examination revealed moderate hirsutism with a score of 15 according to the modified Ferriman-Gallwey scale, androgenic alopecia, dental diastema, macroglossia, and acanthosis. Hormonal analysis demonstrated elevated free testosterone levels on two separate occasions: 8.1 ng/mL (SI: 28 nmol/L) and 6.7 ng/mL (SI: 23.2 nmol/L) (reference range 0.12-0.35 ng/mL [SI 0.42-1.22 nmol/L]); with all other androgenic parameters within the normal range. Imaging studies, including abdominal computed tomography (CT) and transvaginal ultrasound, showed normal adrenal glands and adnexa. Based on clinical suspicion, the patient underwent bilateral adnexectomy. Histopathology confirmed a bilateral ovarian steroid cell tumor, not otherwise specified. Postoperatively, serum testosterone normalized (0.16 ng/mL [SI: 0.55 nmol/L]) within one month with progressive improvement in hirsutism.

We report a rare case of nonclassical 21-hydroxylase deficiency (NC21-OHD) diagnosed in adulthood after being misdiagnosed as polycystic ovary syndrome (PCOS) for 9 years. A 27-year-old Japanese woman presented with longstanding amenorrhea, hirsutism, and polycystic ovarian morphology on ultrasonography but did not exhibit withdrawal bleeding after standard estrogen/progestin (E/P) therapy. Hormonal evaluation revealed a low luteinizing hormone (LH) level, elevated testosterone (T), and a significantly increased 17α-hydroxyprogesterone level, which further increased following adrenocorticotropic hormone stimulation. Genetic analysis identified compound heterozygous mutations in the CYP21A2 gene (c.92C>T; c.293-13C>G), confirming the diagnosis of NC21-OHD. This case underscores the importance of considering NC21-OHD in adolescents and young adults with atypical PCOS features, such as severe hirsutism, abnormal hormonal profiles (low LH with markedly elevated T levels), and resistance to standard E/P therapy.

Statistics from 2024 have shown that 50% of young women use contraception. Nowadays, it is not only used to prevent pregnancy. Positive effects of this treatment can be seen in cases of acne vulgaris, hirsutism, and painful menstruation. A controversial topic is the use of combined oral contraception (COC) in women with migraine with aura - it is contraindicated, but for headaches associated with the menstrual cycle, there is a chance of improvement, especially with the 28/0 regimen. This review assessed differences in the effects of substances contained in COC. Tablets containing ethinylestradiol in combination with drospirenone, levonorgestrel, desogestrel, chlormadinone acetate, dienogest, or lynestrenol were compared. The effects of different drug doses on body mass index (BMI), blood pressure, and the severity of adverse effects in women were considered. An individualized approach to patients is important to select COCs appropriate for the condition and at the same time minimize adverse effects, thereby improving quality of life. The progress in the development of newer COCs, such as an estetrol-containing pill with drospirenone, is promising as well.

Polycystic ovary syndrome (PCOS) is a lifelong endocrine-metabolic condition with prominent dermatologic manifestations such as hirsutism, acne/seborrhea, and female pattern hair loss (FPHL), which are frequently the initial complaint for seeking medical attention.