Abstract Introduction Klinefelter syndrome (KS) is a common sex chromosome aneuploidy in men (47,XXY). Although rarely recognised in childhood and adolescence, a classical description is a patient with gynaecomastia, hypogonadism, and cardiovascular and metabolic abnormalities. Erectile dysfunction (ED), delayed ejaculation (DE) and decreased libido might be manifestations of male hypogonadism in KS, due to testicular dysfunction and androgen deficiency. Nevertheless, these symptoms might be attributable to other conditions, from vascular pathology, such as peripheral arterial disease (PAD), to psychosocial factors, like sexual performance anxiety. Understanding the overlapping mechanisms is essential to provide integrated and effective management, especially in primary care settings where coordination of multidisciplinary care is crucial. Objective To describe a case of ED in a patient with KS, highlighting the multifactorial etiology and the importance of a holistic and multidisciplinary management approach in primary care. Methods A descriptive case report of a 46-year-old male with KS followed in primary care. Clinical data were collected from endocrinology, urology, and vascular appointments between 2003 and 2025. Demographic, clinical, and laboratory information was reviewed, including endocrine and vascular assessments, testosterone replacement regimens, and responses to pharmacologic and psychosexual interventions. Observations focused on the evolution of sexual function, comorbidities, and treatment outcomes. Informed consent was obtained from the patient for publication of this case report. Results In 2003, the patient was found to have primary hypogonadism after bilateral testicular surgery (right radical and left partial orchiectomy for epidermoid cysts), with histology showing a Sertoli-cell-only pattern. Genetic testing later confirmed Klinefelter syndrome (47,XXY). He was on intramuscular testosterone enanthate 250 mg every 15 days. Despite adequate libido under therapy, he reported persistent ED, DE, and sexual performance anxiety. Fluctuations in sexual function corresponded with hormonal peaks and troughs related to injection timing. Comorbidities included dyslipidemia, obesity, and PAD with left popliteal artery occlusion requiring popliteal–tibial bypass. Laboratory results revealed hypergonadotropic hypogonadism, hypertriglyceridemia, and low HDL cholesterol. Treatment with tadalafil and later sildenafil showed inconsistent results. Psychogenic factors such as sexual performance anxiety were identified as aggravating elements. These findings suggest that ED in this patient might be the result of combined androgen deficiency, vascular insufficiency, and psychological distress. Therapeutic strategies considered included switching to alternative testosterone formulations, optimization of cardiovascular risk factors, smoking cessation, nutritional counseling, and psychosexual support. Conclusions This case highlights the multifactorial nature of ED and emphasizes the critical role of interdisciplinary management. A comprehensive approach in primary care, addressing hormonal and vascular status as well as mental health, can significantly improve sexual function and quality of life. Regular assessment of sexual function should be incorporated into routine care, given its substantial impact on overall well-being and the potential for underrecognition in clinical practice, with primary care appointments serving as a cardinal moment for this evaluation. Early recognition and tailored management of ED in KS patients are essential to prevent chronic distress and optimize long-term health outcomes. Disclosure No
Amaral et al. (Mon,) studied this question.