Gender Differences in Clinical Presentation and Treatment Response in Patients with Acromegaly

Backgound: Acromegaly is a rare, chronic endocrine disorder caused in most cases by a growth hormone (GH)-secreting pituitary adenoma, leading to chronic exposure to elevated GH and insulin-like growth factor 1 (IGF-1) levels. Increasing evidence suggests that gender may influence several aspects of acromegaly, including clinical presentation, comorbidities and treatment response. However, available data remain limited and sometimes conflicting. Aim of the study: The aim of this study was to investigate gender-related differences in clinical presentation, comorbidities, treatment patterns and therapeutic outcomes in patients with acromegaly followed at a tertiary referral center. Materials and methods: A retrospective single-center study was performed at the Endocrinology Unit of the University Hospital of Padova. Clinical, biochemical, radiological and therapeutic data were collected from medical records and archived documents of patients with acromegaly. A total of 177 patients were initially evaluated, but after exclusion of patients with insufficient clinical information or alternative diagnoses, 153 patients were included in the final analysis. Variables related to demographic characteristics, disease presentation, pituitary hormone deficiencies, comorbidities, treatment patterns and long-term outcomes were analyzed. Comparison between female and male patients were performed using the Mann-Whitney U test for continuous variables and the chi-square test or Fisher’s exact test for categorical variables. Additional analyses according to menopausal status were also performed. Statistical significance was defined as p < 0.05. Results: The study included 88 females and 65 males. No significant gender differences were observed regarding age at diagnosis, GH and IGF-1 concentrations at diagnosis, tumor size or prevalence of macroadenomas. Significant differences emerged in clinical presentation at diagnosis and associated comorbidities. Sleep-related symptoms were more frequent in males than females (38.5% vs 15.5%, p=0.005), as were obstructive sleep apnea syndrome (41.5% vs 19.5%, p=0.003), hypogonadism (36.9% vs 10.3%, p<0.001) and colon polyps (40.0% vs 20.7%, p=0.009), whereas carpal tunnel syndrome was more prevalent among females (18.3% vs 5.7%, p=0.035). No significant gender differences were observed in treatment strategies or treatment outcomes. Also long-term disease control at the last follow-up was comparable between genders (78.4% of females vs 83.1% of males, p=0.472). Additional analyses according to menopausal status revealed marked heterogeneity among female patients. Premenopausal women showed higher GH concentrations at diagnosis (13.6ng/mL vs 6.4ng/mL, p=0.015), larger tumors (17mm vs 11mm, p=0.010) and a higher prevalence of macroadenomas (87.2% vs 65.8%, p=0.018) compared with postmenopausal women. Conclusions: Gender influences several aspects of the phenotypic expression of acromegaly, particularly clinical manifestations and associated comorbidities, but does not seem to affect the probability of achieving long-term disease control. These findings suggest that gender may have a greater impact on the phenotypic presentation of acromegaly than on its ultimate therapeutic outcome. Furthermore, menopausal status appears to represent an important source of heterogeneity among female patients, with the most striking differences involving biochemical activity and tumor burden. A better understanding of the role of gender and estrogens in acromegaly can contribute to earlier diagnosis, improved screening strategies and more personalized patient management. Further multicenter studies are needed to better define the role of gender and estrogens in the natural history, clinical presentation, comorbidity development and therapeutic response of acromegaly.