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Metabolic syndrome is often associated. True hirsutism and acne should not be considered normal as they may reveal tumorous sources of excessive androgen secretion originating from either the adrenals or the ovaries. Once adrenal causes are excluded, virilizing ovarian tumors must be considered, with Sertoli-Leydig cell tumor being the most common histological subtype. Cases presentations We report the observations of three female patients who presented with post-menopausal hyperandrogenism of ovarian origin during the year 2023, with details on clinical presentation, lab results, and aspects found both on ultrasound and magnetic resonance imaging. They all underwent surgery and two of them were diagnosed with Sertoli-Leydig cell tumors. Conclusion Postmenopausal hyperandrogenism, though rare, requires thorough assessment to avoid misdiagnosis of underlying androgen-secreting tumors, with Sertoli-Leydig cell tumors being the predominant subtype. Surgical intervention is the primary treatment modality, often resulting in complete postoperative recovery. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/14-1078", "name": "Postmenopausal hyperandrogenism of ovarian origin" } } ] } Home Browse Postmenopausal hyperandrogenism of ovarian origin ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Aloui H, AZOUZ E, Boujelbene N et al. Postmenopausal hyperandrogenism of ovarian origin [version 1; peer review: awaiting peer review] . F1000Research 2025, 14 :1078 ( https://doi.org/10.12688/f1000research.163667.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Clinical Practice Article Postmenopausal hyperandrogenism of ovarian origin [version 1; peer review: awaiting peer review] Haithem Aloui https://orcid.org/0000-0002-8569-2186 1 , EYA AZOUZ 1 , Nadia Boujelbene 1 , [...] Ahlem Omri 1 , Hatem Frikha 1 , Rami Hammami https://orcid.org/0009-0000-6030-1372 1 , Amal Chermiti 1 , Ferdaous Ouasli 1 , Hassine Saber Abouda 1 , Badis Chanoufi 1 , Imen Abbes 1 Haithem Aloui https://orcid.org/0000-0002-8569-2186 1 , EYA AZOUZ 1 , [...] Nadia Boujelbene 1 , Ahlem Omri 1 , Hatem Frikha 1 , Rami Hammami https://orcid.org/0009-0000-6030-1372 1 , Amal Chermiti 1 , Ferdaous Ouasli 1 , Hassine Saber Abouda 1 , Badis Chanoufi 1 , Imen Abbes 1 PUBLISHED 13 Oct 2025 Author details Author details 1 Universite de Tunis El Manar Faculte de Medecine de Tunis, Tunis, Tunis, Tunisia Haithem Aloui Roles: Conceptualization, Data Curation, Investigation, Writing – Original Draft Preparation EYA AZOUZ Roles: Data Curation, Methodology, Writing – Original Draft Preparation Nadia Boujelbene Roles: Methodology Ahlem Omri Roles: Methodology Hatem Frikha Roles: Conceptualization, Formal Analysis, Supervision, Writing – Original Draft Preparation Rami Hammami Roles: Investigation Amal Chermiti Roles: Investigation Ferdaous Ouasli Roles: Investigation Hassine Saber Abouda Roles: Formal Analysis, Supervision Badis Chanoufi Roles: Formal Analysis Imen Abbes Roles: Data Curation OPEN PEER REVIEW REVIEWER STATUS AWAITING PEER REVIEW This article is included in the Oncology gateway. This article is included in the The Multifaceted Aspects of Menopause collection. Abstract Introduction During the postmenopausal period, hyperandrogenic manifestations include hirsutism and variable degrees of virilization. Metabolic syndrome is often associated. True hirsutism and acne should not be considered normal as they may reveal tumorous sources of excessive androgen secretion originating from either the adrenals or the ovaries. Once adrenal causes are excluded, virilizing ovarian tumors must be considered, with Sertoli-Leydig cell tumor being the most common histological subtype. Cases presentations We report the observations of three female patients who presented with post-menopausal hyperandrogenism of ovarian origin during the year 2023, with details on clinical presentation, lab results, and aspects found both on ultrasound and magnetic resonance imaging. They all underwent surgery and two of them were diagnosed with Sertoli-Leydig cell tumors. Conclusion Postmenopausal hyperandrogenism, though rare, requires thorough assessment to avoid misdiagnosis of underlying androgen-secreting tumors, with Sertoli-Leydig cell tumors being the predominant subtype. Surgical intervention is the primary treatment modality, often resulting in complete postoperative recovery. READ ALL READ LESS Keywords Postmenopausal, Hyperandrogenism, Virilization, Hyperthecosis, Ovarian tumor, Sertoli-Leydig cell tumor, Imaging Corresponding Author(s) Haithem Aloui ( [email protected] ) Close Corresponding author: Haithem Aloui Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Aloui H et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Aloui H, AZOUZ E, Boujelbene N et al. Postmenopausal hyperandrogenism of ovarian origin [version 1; peer review: awaiting peer review] . F1000Research 2025, 14 :1078 ( https://doi.org/10.12688/f1000research.163667.1 ) First published: 13 Oct 2025, 14 :1078 ( https://doi.org/10.12688/f1000research.163667.1 ) Latest published: 13 Oct 2025, 14 :1078 ( https://doi.org/10.12688/f1000research.163667.1 ) Introduction During the postmenopausal period, hyperandrogenic manifestations include hirsutism and variable degrees of virilization. Metabolic syndrome is often associated. The literature on virilizing ovarian tumors remains mostly limited to case reports. Sertoli- Leydig cell tumor is the most common histological subtype. 1 Treatment is surgery and complete post-operative recovery is often observed. We report the observations of three female patients who presented with post-menopausal hyperandrogenism of ovarian origin during the year 2023. Case presentation 1 A 62-year-old female patient, Gravida 1 Para 1, menopausal at the age of 55, with a personal history of type 2 diabetes and hypertension, presented with signs of virilization discovered 3 years prior. On clinical examination, the patient was overweight with a body mass index calculated at 28 kg per m 2 and an android-type fat distribution. Fronto-temporal alopecia and clitoral hypertrophy were noted with a Ferriman and Gallwey Score estimated at 23 ( Figure 1 ). Figure 1. Photograph of a 62-year-old woman presenting with hirsutism with excessive hair growth on the upper lip and chin (A) and clitoral hypertrophy (B). Laboratory studies revealed very high testosterone levels at 4.7 nmol/l, rechecked several times (N:0.2-3.5 nmol/l), normal levels of CA 125, DHEA-S and normal corticotropic balance with good dexamethasone control. A pelvic ultrasound was performed showing bilateral well defined hypoechoic round solid ovarian masses ( Figure 2 ). Figure 2. Pelvic ultrasound image showing bilateral hypoechoic solid ovarian masses. Vascularity is noted (not shown). No calcification, ascites or retroperitoneal lymphadenopathy were found. On MRI, bilateral, round solid ovarian masses with homogenous low signal intensity on T2 were found. These masses were classified as ORADS category 2. No adrenal mass was noted ( Figure 3 ). Figure 3. A: Axial T1-weighted post contrast MR image showing mild enhancement of the ovarian masses (arrows). B: Axial T2-weighted MR image showing bilateral well-circumscribed hypointense ovarian masses (arrows). The patient underwent a total hysterectomy and bilateral adnexectomy with clitoral reduction ( Figure 4 ). Figure 4. A: Photograph showing hysterectomy and bilateral adnexectomy piece. B: Photograph showing ovarian enlargement noticed during surgery. Pathologic report showed a morphological aspect that suggests bilateral ovarian fibroids or ovarian stromal hyperplasia ( Figure 5 ). No findings suggestive of hyperthecosis were reported. Clitoris histological examination found no tumor proliferation. Figure 5. Microscopic examination of an ovarian fibroma. A: Microscopic examination with 200x magnification shows proliferation of spindle cells arranged in intersecting bundles. B: Microscopic examination with 400x magnification shows cells with spindle to ovoid nuclei with scant cytoplasm and no mitotic activity. On follow up, complete recovery was noted with a decrease in levels of testosterone <0.7 nmol/l. Case presentation 2 A 70-year-old female patient, Gravida 6 Para 5, menopausal at the age of 53, with a personal history of hypertension and android-type obesity, presented with severe hirsutism, alopecia, and clitoral hypertrophy ( Figure 6 ) with a Ferriman and Gallwey Score estimated at 28. Testosterone level was high at 1.5 μg/L along with D4A levels (2.3 μg/L), AFP levels at 2.42 (<7 ng/ml) and CA 19-9 levels at 29.84 IU/l. Figure 6. Photograph showing clitoral hypertrophy. Pelvic ultrasound showed an enlarged uterus and right ovary (measured at 60*30 mm). MRI revealed an enlarged right ovary, with several follicles as well as a solid mass with intermediate signal on T2 and avid enhancement after gadolinium administration. The left ovary was of normal size 26*24 mm. No mass was found ( Figure 7 ). Figure 7. A: Axial T1-weighted post contrast MR image showing avid enhancement the mass (arrow). B: Axial T2-weighted MR image showing a right ovarian well-circumscribed solid mass with intermediate signal (arrow). The patient underwent surgery with hysterectomy, bilateral adnexectomy, peritoneal cytology and peritoneal biopsies ( Figure 8 ). Figure 8. Photograph showing macroscopic appearance of the right ovary during surgery. Histology results were compatible with a right ovarian fibroma with associated hyperplasia of Leydig cells, given the clinical signs of hyperandrogenism, the morphological aspects and the immunohistochemical profile ( Figures 9 and 10 ). Figure 9. Microscopic examination of an ovarian fibroma with hyperplasia of Leydig cells. A: Microscopic examination with 200x magnification shows spindle cells proliferation with clusters of Leydig cells. B: Microscopic examination with 400x magnification shows large polygonal cells with eosinophilic non granular cytoplasm and large round nuclei and prominent nucleoli consistent with Leydig cells. Figure 10. Immunohistochemistry testing positive for inhibin (A) and calretinin (B) in Leydig cells’ clusters. Upon follow-up, there was observed a complete remission, with testosterone levels decreasing to below 0.7 nmol/l. Case presentation 3 A 60-year-old female patient, nulligest, menopausal at the age of 54, with a personal history of hypertension, type IIb dyslipidaemia and long-standing insulin treated type 2 diabetes with associated degenerative complications, presents with hirsutism ( Figure 11 ), androgenic alopecia, excessive sweating, and increased libido. Ferriman and Gallwey score was estimated at 26 with signs of virilization (muscle hypertrophy and male-pattern baldness). Figure 11. Photograph showing excessive hair growth in the forearm in a 60-year-old female patient. Testosteronemia was at 9.22 nmol/l with normal levels of SDHEA (873 ng/ml). Lab tests revealed a normal basic cortisol level with no findings suggestive of cushing’s syndrome. A Thoraco-abdominopelvic CT was performed showing a 30mm right adrenal mass with spontaneous density at 7 HU and an absolute wash out at 35% suggestive of an adenoma. Pelvic MRI revealed a solid left ovarian mass with heterogeneous signal on T2 with an intermediate risk time intensity curve (B) on dynamic contrast enhancement, classified as ORADS category 4 ( Figure 12 ). Figure 12. Axial T2-weighted MRI image showing a left ovarian mass with heterogeneous high signal intensity (arrow). The patient underwent left adnexectomy ( Figure 13 ). Figure 13. Macroscopic image of the left ovarian mass after extraction. Histology found a fleshy, brownish, and friable nodular formation, with a well-circumscribed tumor proliferation made of large polyhedral or rounded epithelioid cells with abundant eosinophilic cytoplasm sometimes including dense, elongated rod-shaped eosinophilic crystals (Reinke crystals). The nuclei were monomorphic, rounded and nucleolated. They were frequently grouped into clusters leaving free eosinophilic cytoplasmic intervals. No tumor necrosis or capsular rupture was found. Therefore, it concluded to a benign Leydig cell tumor of the ovary ( Figure 14 ). Figure 14. Cell clusters separated by free eosinophilic cytoplasmic intervals (A) and Reinke crystals. During follow-up, there was observed full resolution accompanied by a reduction in testosterone levels to <0.7 nmol/l. Discussion The diagnosis of a tumorous origin of hyperandrogenism after menopause is mainly based on the rapid onset, progression, and severity of clinical symptoms. 1 Thus, recent, and severe signs of virilization such as baldness, clitoral hypertrophy and deepening of the voice are in favor of a tumorous source of excessive androgen secretion. In our patients, the absence of hyperandrogenism in pre-menopause, the rapid progression over the years, as well as the presence of signs of virilization are clinical arguments in favor of a tumor etiology. Based on the consensus of the French Society of Endocrinology, when testosterone levels are high, blood testing of SDHEA (dehydroepiandrosterone sulfate) must be performed and increased levels may point to an adrenal cause. 2 In the study by Elhassan YSla et al, normal SDHEA levels did not exclude the diagnosis of adrenocorticaloma. Furthermore, high levels of SDHEA were found in cases of hyperandrogenism of ovarian origin. 3 In pre- and post-menopausal women, the two sources of androgen secretion are the ovaries and the adrenal glands. Imaging and more specifically adrenal CT and pelvic MRI are the most appropriate tools that may allow the identification of the etiology and therefore help establish a final diagnosis. 4 Sertoli-Leydig cell tumors constitute less than 1% of overall ovarian tumors with 10% of them being well-differentiated and 90% moderately and poorly differentiated tumors. 5 , 6 Sertoli-Leydig cell tumors usually occur in young women but can also occur in postmenopausal women. In studies, the mean age at diagnosis was 24 years. 7 Women with well-differentiated Sertoli-Leydig cell tumors are, on average, 40 years old, 10 to 15 years older than those with moderately or poorly differentiated tumors. 8 , 9 In our series, all women were postmenopausal. Two of them were diagnosed Sertoli-Leydig cell tumors. Approximately 50% of Sertoli-Leydig cell tumors produce steroid hormones, and 40% of patients are virilized. Patients present with different symptoms of virilization which are evaluated using the Ferriman and Gallewey score. 10 Sertoli-Leydig cell tumors tend to be unilateral and confined to the ovary (stage IA) at diagnosis. Unilateral salpingo-oophorectomy is the main treatment for most patients. 11 , 12 Hysterectomy and bilateral salpingo-oophorectomy may be suggested for older patients. Lymph node metastases are exceptional. Regression of symptoms usually follows tumor removal. 13 Well-differentiated Sertoli-Leydig cell tumor is a clinically benign tumor that does not recur after complete excision. The prognosis is usually good for patients with moderately and poorly differentiated Sertoli-Leydig cell tumors. 14 In our series, patients underwent total hysterectomy with bilateral adnexectomy with complete recovery on follow up. Conclusion Hyperandrogenism after menopause is a rare condition that needs careful evaluation in order not to misdiagnose an underlying androgen-secreting tumors. Sertoli-Leydig cell tumors is the most common subtype of virilizing ovarian tumors. Treatment is surgery and complete post-operative recovery is often observed. Consent Written informed consent for publication of the clinical details and/or clinical images was obtained from the patients or their legal guardians. All identifiable information has been anonymized to protect patient confidentiality. Data availability All data underlying the results are available as part of the article and no additional source data are required. References 1. Markopoulos MC, Kassi E, Alexandraki KI, et al. : Hyper-androgenism after menopause. Eur. J. Endocrinol. 2015; 172 (2): R79–R91. Publisher Full Text 2. Pugeat M, Déchaud H, Raverot V, et al. : Recommendations for investigation of hyperandrogenism. Ann. Endocrinol. (Paris). 2010; 71 (1): 2–7. Publisher Full Text 3. Elhassan YS, Idkowiak J, Smith K, et al. : Causes, patterns, and severity of androgen excess in 1205 consecutively recruited women. J. Clin. Endocrinol. Metab. 2018; 103 (3): 1214–1223. PubMed Abstract | Publisher Full Text | Free Full Text 4. Sarfati J, Moraillon-Bougerolle M, Christin-Maitre S: Une hyperandrogénie chez la femme ménopausée: origine ovarienne ou origine surrénalienne ? Gynecol Obstet Fertil Senol. 2022; 50 (10): 675–681. PubMed Abstract | Publisher Full Text 5. Young RH, Scully RE: Ovarian Sertoli-Leydig cell tumors. A clinicopathological analysis of 207 cases. Am. J. Surg. Pathol. 1985; 9 : 543–569. Publisher Full Text 6. Zaloudek C, Norris HJ: Sertoli-Leydig tumors of the ovary. A clinicopathologic study of 64 intermediate and poorly differentiated neoplasms. Am. J. Surg. Pathol. 1984; 8 : 405–418. PubMed Abstract | Publisher Full Text 7. Sehemby M, Bansal P, Sarathi V, et al. : Virilising ovarian tumors: a single-center experience. Endocr. Connect. 2018; 7 (12): 1362–1369. PubMed Abstract | Publisher Full Text 8. The WHO Classification of Tumours Editorial Board: World Health Organization classification of tumours. Female genital tumours. IARC; 5th ed.2020. 9. Gressel GM, Buza N, Pal L: Ovarian Sertoli-Leydig cell tumors: a single institution experience and review of the literature. Eur. J. Gynaecol. Oncol. 2017; 38 : 214–220. 10. Baba AI, Câtoi C: Chapter 10, FEMALE GENITAL TRACT TUMORS. Comparative Oncology. Bucharest (RO): The Publishing House of the Romanian Academy; 2007. 11. Sigismondi C, Gadducci A, Lorusso D, et al. : Ovarian Sertoli-Leydig cell tumors: a retrospective MITO study. Gynecol. Oncol. 2012; 125 : 673–676. PubMed Abstract | Publisher Full Text 12. Gui T, Cao D, Shen K, et al. : A clinicopathological analysis of 40 cases of ovarian Sertoli-Leydig cell tumors. Gynecol. Oncol. 2012; 127 : 384–389. PubMed Abstract | Publisher Full Text 13. Fresneau B, Orbach D, Faure-Conter C, et al. : Sex-cord stromal tumors in children and teenagers: results of the TGM-95 study. Pediatr. Blood Cancer. 2015; 62 : 2114–2119. PubMed Abstract | Publisher Full Text 14. Young RH, Scully RE: Well-differentiated ovarian Sertoli-Leydig cell tumors: a clinicopathological analysis of 23 tumors. Int. J. Gynecol. Pathol. 1984; 3 : 277–290. Publisher Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 13 Oct 2025 ADD YOUR COMMENT Comment Author details Author details 1 Universite de Tunis El Manar Faculte de Medecine de Tunis, Tunis, Tunis, Tunisia Haithem Aloui Roles: Conceptualization, Data Curation, Investigation, Writing – Original Draft Preparation EYA AZOUZ Roles: Data Curation, Methodology, Writing – Original Draft Preparation Nadia Boujelbene Roles: Methodology Ahlem Omri Roles: Methodology Hatem Frikha Roles: Conceptualization, Formal Analysis, Supervision, Writing – Original Draft Preparation Rami Hammami Roles: Investigation Amal Chermiti Roles: Investigation Ferdaous Ouasli Roles: Investigation Hassine Saber Abouda Roles: Formal Analysis, Supervision Badis Chanoufi Roles: Formal Analysis Imen Abbes Roles: Data Curation Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. 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