Claudia Nacea-Radu

This study aims to synthesize contemporary evidence on the benefits, risks, and emerging options in menopausal hormone therapy (MHT), emphasizing the recent literature. A narrative review of peer-reviewed studies and guidelines (up to September 2025) from major databases (e.g., MEDLINE/PubMed, Embase, Cochrane) was conducted, with emphasis on the last five years and qualitative synthesis. MHT provides the most effective relief of vasomotor symptoms and is the first-line treatment for genitourinary syndrome of menopause, particularly with the use of low-dose local vaginal estrogen preparations; it also prevents early postmenopausal bone loss and reduces fractures in selected cases. Cardiovascular prevention is not an indication. Benefit–risk depends on timing, route, and dose. Initiation within 10 years of menopause as well as the use of transdermal estradiol at low–moderate doses are favored when cardiometabolic or thrombotic risk is salient. In contrast, oral regimens—particularly those using conjugated equine estrogens—are associated with higher risks of venous thromboembolism and stroke compared with transdermal 17 β-estradiol, and risk also varies by the type of progestogen used. Effects on breast cancer risks are regimen-specific: neutral to favorable with estrogen-alone after hysterectomy, but increasing with longer use of combined therapy. While the absolute risk of ovarian cancer remains small, evidence for colorectal cancer remains mixed. MHT confers modest improvements in sleep, mood, intercourse, and quality of life. Estetrol (E4) shows anti-VMS efficacy at the minimum effective oral dose and favorable pharmacology, but conclusive data on its long-term cardiovascular, thrombotic, and breast safety are pending. MHT should be individualized appropriately based on the patient, timing, route, dose, and choice of progestogen. The lowest effective dose should be used, alongside periodically reassessing the therapy as new evidence, including emerging data on E4, emerges.

Background: Feminizing adrenocortical tumors (FATs) are an exceedingly rare subset of adrenal neoplasms, typically affecting adult men and characterized by an excess of estrogen, suppressed gonadotropins, and gynecomastia. Most FATs are malignant, with a poor prognosis and a high risk of recurrence. Case Presentation: We report the case of a 24-year-old male with bilateral gynecomastia, abdominal mass symptoms, and one year of unexplained infertility. A hormonal evaluation revealed elevated estradiol (90.1 pg/mL) and suppressed ACTH (2.6 pg/mL), with inappropriately normal cortisol levels (12.1 µg/dL). Imaging identified a right adrenal mass. The patient underwent open adrenalectomy, and histopathology confirmed stage II adrenocortical carcinoma (T2NxM0) with autonomous estradiol secretion, negative margins, and a Ki-67 index of 10%. Postoperatively, gonadal function normalized, and infertility resolved at two months. The multidisciplinary tumor board considered but did not initiate adjuvant mitotane, given the completely resected low-stage disease. Conclusions: This case illustrates the rare presentation of feminizing adrenocortical carcinoma with reversible infertility and highlights the importance of early recognition and close surveillance. In addition, our literature review of 12 male cases reported between 2015 and 2025 emphasizes gynecomastia as the hallmark presentation and discusses emerging evidence supporting active surveillance as a potential alternative to adjuvant mitotane in selected low-risk patients.

Feminizing adrenocortical tumors (FATs) represent an exceedingly rare subset of primary adrenal neoplasms, characterized by elevated estrogen levels and suppressed gonadotrophin concentrations. These tumors predominantly affect adult males and are commonly associated with clinical manifestations such as gynecomastia, features of hy-pogonadism and unintended weight loss. The vast majority of FATs are malignant in nature, exhibiting an unfavorable prognosis and a high likelihood of recurrence. We present the case of a 24-year-old male diagnosed with adrenocortical carcinoma, characterized by elevated estrogen levels (90.1 pg/mL), who initially presented with symptoms related to abdominal mass effect and bilateral gynecomastia. Notably, the patient reported one year of unexplained infertility, which resolved spontaneously postoperatively at three months following surgical intervention. Another distinctive feature of this case was the patient's adrenal hormonal profile, which revealed suppressed ACTH (2.6 pg/mL) in the presence of inappropriately normal cortisol levels (12,1 ug/dL). The patient underwent right adrenalectomy, and histo-pathological along with immunohistochemical analyses confirmed a diagnosis of stage II adrenocortical carcinoma (T2, Nx, M0) with autonomous estradiol production. The case was reviewed by a multidisciplinary tumor board for consideration of mitotane therapy; however, the patient was not enrolled due to a completely resected stage T2NxM0 adrenocortical carcinoma with negative margins and a Ki-67 index of 10%. This case underscores the rare presentation of feminizing adrenocortical carcinoma and emphasizes the importance of early diagnosis and close postoperative surveillance, given the tumor’s high recurrence potential. In addition, we conducted a systematic review of the literature from 2015 to 2025, identifying 12 male cases of estrogen-secreting adrenocortical carcinoma (ES-ACC) pre-senting initially with gynecomastia. Data on presentation, hormonal profile, treatment, recurrence and survival were analyzed. Our review highlights a potential paradigm shift in the management of selected low-risk ACC cases, where active surveillance may rep-resent a safe and effective alternative to adjuvant mitotane therapy.