Diana Loreta Paun

Background and Objectives: Young women treated for breast cancer often face persistent sexual and reproductive challenges post-treatment, which frequently remain unaddressed during routine follow-up. This study evaluated health-related quality of life (HRQoL), sexual health, and fertility-related counselling in breast cancer survivors younger than 40 years. Materials and Methods: We performed a single-centre cross-sectional study including 65 women with non-metastatic breast cancer (at least 12 months post-primary treatment). Patients completed the EORTC QLQ-C30 and SHQ-22 questionnaires, along with a pilot-tested 7-item fertility preservation survey. Data were analyzed using descriptive statistics and non-parametric tests to compare treatment subgroups (e.g., endocrine therapy vs. others). Results: Overall quality-of-life scores were relatively preserved (median 66.67), with high functional scores. However, patients reported symptomatic distress, particularly fatigue and insomnia (both median 33.33). Sexual health was significantly impacted: communication with healthcare professionals was the most impaired domain (median score 100), followed by low libido (66.7) and vaginal dryness (66.7). Women receiving endocrine therapy reported significantly lower functional scores and a higher symptom burden compared to those not on endocrine treatment (p < 0.05). While 60% of patients received fertility information, only 16.9% underwent preservation procedures. Notably, a significant association was observed between reproductive health actions and sexual behaviour; women who had undergone fertility preservation procedures reported higher levels of sexual activity (p = 0.015). Conclusions: Despite relatively preserved functional status, young breast cancer survivors face significant symptomatic and sexual challenges. The profound lack of communication regarding sexual health and the gaps in fertility counselling highlight the need for a more integrative, multidisciplinary approach in survivorship care.

Background/Objectives: Type 2 diabetes (T2DM) and hypothyroidism often coexist, worsening cardiometabolic risk. Oral semaglutide and levothyroxine each improve metabolic parameters, but the effect of combined therapy is understudied. This study aimed to evaluate whether oral semaglutide administered concomitant with levothyroxine provides additive benefits on lipid profile, glycemic control, and body weight in patients with both conditions. Methods: This prospective comparative observational study assessed a total of 210 patients who were enrolled (70 per group) with a 6-month follow-up. Group A (T2DM and hypothyroidism) received semaglutide and levothyroxine, group B (hypothyroidism only) received levothyroxine, and group C (T2DM only) received oral semaglutide. Lipid profile, glycemic profile (HbA1c), thyroid profile, and anthropometric parameters were comparable across groups at baseline and after 6 months. Results: Group A demonstrated significant improvements in lipid parameters: LDL-cholesterol decreased by 12.7%, HDL increased by 9.0%, and triglycerides decreased by 6.7% (all comparisons p < 0.001 unless otherwise specified). In contrast, group B experienced worsening lipid profiles (LDL increased by 11.0%, HDL decreased by 0.5%, and triglycerides increased by 9.1%), while group C showed modest changes (LDL increased by 4.5%). Glycemic control improved among diabetic patients, with HbA1c declining by 7.7% in group A and 12.6% in group C. Body mass index (BMI) decreased in groups A (4.9%) and C (6.0%). Conclusions: The concurrent administration of oral semaglutide and levothyroxine produces additive cardiometabolic advantages in individuals with T2DM and hypothyroidism. These findings suggest that combined treatment may optimize metabolic outcomes in this particularly high-risk population.

Triple-negative breast cancer (TNBC) is an aggressive malignancy that disproportionately affects young women. The integration of immune checkpoint inhibitors (ICIs) has significantly improved outcomes in both early-stage and metastatic TNBC, shifting attention toward long-term survivorship issues, particularly endocrine function and fertility. However, the reproductive safety profile of ICIs remains insufficiently characterized. This narrative review synthesizes current preclinical and clinical evidence on ICI-associated reproductive toxicity, focusing on both direct immune-mediated gonadal injury and indirect disruption of the hypothalamic–pituitary–gonadal axis. Experimental models consistently demonstrate immune cell infiltration of ovarian and testicular tissue, cytokine-driven inflammatory cascades, follicular atresia, impaired spermatogenesis, and altered steroidogenesis following PD-1/PD-L1 and CTLA-4 blockade. Emerging clinical data report cases of immune-related orchitis, azoospermia, testosterone deficiency, diminished ovarian reserve, and premature ovarian insufficiency. Secondary hypogonadism due to immune-mediated hypophysitis represents an additional and frequently underdiagnosed mechanism. We further discuss the oncofertility challenges faced by young patients with TNBC treated with chemoimmunotherapy, emphasizing the uncertainty of fertility risk stratification and the importance of early fertility counseling and individualized fertility preservation strategies. To illustrate the potential clinical impact, we present the case of a 34-year-old nulliparous woman who developed premature ovarian insufficiency two years after neoadjuvant chemoimmunotherapy including atezolizumab, despite ovarian suppression. In conclusion, while ICIs have transformed the therapeutic landscape of TNBC, their potential long-term impact on reproductive and endocrine health represents a clinically significant concern. A precautionary, multidisciplinary oncofertility approach and prospective clinical registries are essential to define the true incidence and mechanisms of ICI-associated reproductive toxicity.

Triple-negative breast cancer (TNBC) is an aggressive malignancy that disproportionately affects young women. The integration of immune checkpoint inhibitors (ICIs) has significantly improved outcomes in both early-stage and metastatic TNBC, shifting attention toward long-term survivorship issues, particularly endocrine function and fertility. However, the reproductive safety profile of ICIs remains insufficiently characterized. This narrative review synthesizes current preclinical and clinical evidence on ICI-associated reproductive toxicity, focusing on both direct immune-mediated gonadal injury and indirect disruption of the hypothalamic–pituitary–gonadal axis. Experimental models consistently demonstrate immune cell infiltration of ovarian and testicular tissue, cytokine-driven inflammatory cascades, follicular atresia, impaired spermatogenesis, and altered steroidogenesis following PD-1/PD-L1 and CTLA-4 blockade. Emerging clinical data report cases of immune-related orchitis, azoospermia, testosterone deficiency, diminished ovarian reserve, and premature ovarian insufficiency. Secondary hypogonadism due to immune-mediated hypophysitis represents an additional and frequently underdiagnosed mechanism. We further discuss the oncofertility challenges faced by young patients with TNBC treated with chemoimmunotherapy, emphasizing the uncertainty of fertility risk stratification and the importance of early fertility counseling and individualized fertility preservation strategies. To illustrate the potential clinical impact, we present the case of a 34-year-old nulliparous woman who developed premature ovarian insufficiency two years after neoadjuvant chemoimmunotherapy including atezolizumab, despite ovarian suppression. In conclusion, while ICIs have transformed the therapeutic landscape of TNBC, their potential long-term impact on reproductive and endocrine health represents a clinically significant concern. A precautionary, multidisciplinary oncofertility approach and prospective clinical registries are essential to define the true incidence and mechanisms of ICI-associated reproductive toxicity.

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.

Tertiary hyperparathyroidism (THPT) arises in patients with chronic kidney disease (CKD) as a consequence of prolonged secondary hyperparathyroidism and is marked by autonomous parathyroid hormone (PTH) secretion. In some cases, parathyroid hyperplasia persists even after successful renal transplantation, resulting in sustained PTH elevation and hypercalcaemia. These alterations contribute to bone loss, vascular calcification, and increased cardiovascular risk. Management includes medical therapy with calcimimetics or vitamin D analogues and surgical intervention via parathyroidectomy. However, optimal timing and treatment strategy remain uncertain. This review examines the pathophysiology, clinical manifestations, and current management paradigms of THPT, with an emphasis on areas that require further research and consensus.

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.

The widespread use of advanced imaging techniques has led to a rising incidence of adrenal incidentalomas (AIs), asymptomatic adrenal masses discovered during imaging for non-adrenal-related conditions. AIs represent a diagnostic and therapeutic challenge due to their varied etiology, secretory potential, and potential for malignancy. This review aims to provide a comprehensive overview of the current knowledge on adrenal incidentalomas, focusing on their pathogenesis, diagnostic work-up, imaging features, hormonal evaluation, and evidence-based management, with a special emphasis on autonomous cortisol secretion (ACS). A thorough narrative review of the literature from the past two decades was conducted, synthesizing data from key international guidelines (ESE/ENSAT), observational studies, meta-analyses, and case series regarding the evaluation and treatment of AI. AI represents an increasingly relevant clinical condition requiring a multidisciplinary, personalized approach. Prompt endocrine and radiological evaluation is essential to identify hormonally active or potentially malignant tumors. The complexity of the natural history of AI and the evolving understanding of ACS underline the need for tailored follow-up and management strategies.

Background: Breast cancer is the most frequently diagnosed cancer in women, and advances in genetic screening have led to a growing number of patients being identified as BRCA mutation carriers. For these women, the safety of pregnancy following cancer treatment remains insufficiently studied, and possible biological mechanisms—including defective DNA repair pathways and accelerated depletion of the ovarian reserve—may influence fertility potential and pregnancy outcomes. This exploratory research set out to examine whether BRCA status impacts reproductive outcomes in breast cancer survivors, while also considering underlying biological explanations for any observed differences. Methods: We performed a retrospective, single-institution cohort study involving young women with non-metastatic breast cancer who had undergone BRCA testing over a 17-year period. Clinical, oncologic, and reproductive data were collected and patients were followed longitudinally. Results: Of the 117 women who met eligibility criteria, 15 conceived at least once after cancer therapy; 11 carried no BRCA mutation, and 4 were BRCA-positive (2 with BRCA1 and 2 with BRCA2 variants). While the overall cohorts were broadly comparable, significant differences emerged in terms of tumor grade, hormone receptor status, HER2 expression, and treatment modalities. BRCA mutation status did not appear to influence reproductive outcomes, and all pregnancies in both groups progressed to full-term delivery without major obstetric complications or congenital anomalies. Conclusions: Within the limitations of a small, retrospective, single-center dataset without adjustment for confounding variables, these preliminary findings suggest that pregnancy after breast cancer may be safe for BRCA mutation carriers, with no apparent adverse effect on maternal prognosis or birth outcomes. Confirmation from larger, prospective, multicenter studies is essential to validate these results, clarify possible biological mechanisms, and inform evidence-based fertility counseling and survivorship planning for this patient population.

Tertiary hyperparathyroidism (THPT) arises in patients with chronic kidney disease (CKD) as a consequence of prolonged secondary hyperparathyroidism and is marked by autonomous parathyroid hormone (PTH) secretion. In some cases, parathyroid hyperplasia persists even after successful renal transplantation, resulting in sustained PTH elevation and hypercalcaemia. These alterations contribute to bone loss, vascular calcification, and increased cardiovascular risk. Management includes medical therapy with calcimimetics or vitamin D analogues and surgical intervention via parathyroidectomy. However, optimal timing and treatment strategy remain uncertain. This review examines the pathophysiology, clinical manifestations, and current management paradigms of THPT, with an emphasis on areas that require further research and consensus.