Polycystic Ovary Syndrome in the Context of Pituitary Adenomas: Prevalence, Pathophysiology and Clinical Management.

Objective: Many review articles have explored data regarding the coexistence of specific types of pituitary adenomas (PAs) and polycystic ovary syndrome (PCOS), particularly focusing on the potential pathogenesis of this intersection and overlapping features. However, a comprehensive evaluation encompassing the full spectrum of PAs and their association with PCOS remains lacking. This review aims to provide a broad assessment of the interactions between these entities, emphasizing pathophysiological mechanisms, clinical presentations, diagnostic challenges and therapeutic implications.

Methods: A comprehensive literature search was conducted in the PubMed/MEDLINE database, focusing primarily on publications from the years 2000 to 2024, while also including seminal papers from the 1950s. The reference lists of selected articles were also manually searched. Inclusion criteria encompassed review articles, retrospective studies, clinical trials, case reports and meta-analyses providing data on the pathogenesis, clinical features, diagnostic challenges and therapeutic approaches related to PCOS and different PAs.

Results: PCOS and functioning PAs often exhibit overlapping clinical features, complicating diagnosis and management. PCOS may precede and delay the diagnosis of growth hormone (GH)-secreting adenomas. The prevalence of PCOS or its features in acromegaly is influenced by disease activity, while approximating 13% in cases with controlled disease. Excess GH and insulin-like growth factor 1 (IGF-1) adversely affect ovarian function through direct pathways and by inducing insulin resistance, contributing to acromegaly-associated PCOS. In Cushing's syndrome (CS), findings consistent with PCOS may be present in 46% of patients, with cortisol excess contributing to menstrual dysfunction, hyperandrogenism and insulin resistance. While the prevalence of PCOS in patients with prolactinomas remains under-researched, recent studies indicate a 2.8%-10% prevalence of prolactinomas in PCOS. Elevated prolactin (PRL) levels in these patients may promote insulin resistance, further contributing to PCOS pathogenesis. Moreover, increased androgen bioavailability may be observed in all three aforementioned adenomas. To date, no studies have provided prevalence data for PCOS in other types of PAs.

Conclusions: Distinct clinical features, along with biochemical evaluations and imaging, can help differentiate the presence of both PAs and PCOS. Moreover, excluding other mimicking disorders is essential for an accurate diagnosis of PCOS. The persistence or recurrence of menstrual dysfunction, hyperandrogenism and metabolic disturbances in patients with controlled functioning adenomas may indicate a coexisting PCOS diagnosis. Timely diagnosis may optimize management and improve long-term outcomes for both conditions. Future studies should focus on investigating the clinical differences between patients with co-occurring PCOS and PAs compared to those with PCOS alone, ideally in larger cohorts, to better understand unique diagnostic and therapeutic considerations.