Clinical Endocrinology

‘Bone Health—Across a Woman's Lifespan’

ABSTRACTDespite a high burden of osteoporosis and minimal trauma fractures worldwide, there is still a treatment gap in timely diagnosis and optimal treatment. There is also a lack of international consensus and guidelines on the management of bone fragility in premenopausal women. This review article provides an overview of the current understanding of factors impacting women's bone health across the adult lifespan, as well as dilemmas in the diagnosis, assessment and management of osteoporosis in premenopausal and postmenopausal women, premature ovarian insufficiency and bone health following breast cancer.

The impact of ageing and menopause in women with polycystic ovary syndrome

AbstractPolycystic ovary syndrome (PCOS) is a common hormonal, metabolic and reproductive disorder. Women with PCOS at reproductive age have increased risk and prevalence of prediabetes and diabetes and have multiple risk factors for cardiometabolic disease and other comorbidities such as obstructive sleep apnoea, endometrial cancer and mood disorders, which contribute to the overall health burden of the syndrome. However, little is known about the impact of PCOS on long‐term health in ageing women. In this review, we aimed to give an updated overview regarding the long‐term health outcomes of PCOS and their clinical implications in peri‐ and postmenopause. The PCOS phenotype ameliorates with ageing and limited available data suggest that there is no further deterioration in cardiometabolic profile in women with PCOS after menopause. Accordingly, the risk of cardiovascular disease in ageing women with PCOS seems to be no different from those without PCOS and lower than previously anticipated based on their risk during reproductive years. Regarding other comorbidities including sleep apnoea, mood disorders and endometrial cancer, it is difficult to determine the true risk in older women with PCOS due to the confounding factors and lack of long‐term cohort studies. Large, prospective studies on community‐based and well‐phenotyped PCOS cohorts with extended follow‐up into late menopause are needed to confirm these findings.

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

ABSTRACTObjectiveMany 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.MethodsA 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.ResultsPCOS 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.ConclusionsDistinct 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.

Undetectable anti‐Mullerian hormone and inhibin B do not preclude the presence of germ cell tumours in 45,X/46,XY or 46,XY gonadal dysgenesis

AbstractObjectiveIndividuals with 45,X/46,XY or 46,XY gonadal dysgenesis are at increased risk of germ cell malignancies. Therefore, prophylactic bilateral gonadectomy is advised in girls and considered in boys with atypical genitalia for undescended, macroscopically abnormal gonads. However, severely dysgenetic gonads may not contain germ cells rendering gonadectomy unnecessary. Therefore, we investigate if undetectable preoperative serum anti‐Müllerian hormone (AMH) and inhibin B can predict the absence of germ cells, (pre)malignant or otherwise.Design, Patients and MeasurementsIndividuals who had undergone bilateral gonadal biopsy and/or gonadectomy because of suspected gonadal dysgenesis in 1999–2019 were included in this retrospective study if preoperative AMH and/or inhibin B were available. Histological material was reviewed by an experienced pathologist. Haematoxylin and eosin and immunohistochemical stainings for SOX9, OCT4, TSPY and SCF (KITL) were used.ResultsThirteen males and 16 females were included, 20 with 46,XY and 9 with 45,X/46,XY DSD. Three females had dysgerminoma alongside gonadoblastoma; two gonadoblastoma, one germ cell neoplasia in situ (GCNIS) and three males had pre‐GCNIS and/or pre‐gonadoblastoma. Gonadoblastoma and/or dysgerminoma were present in 3/11 individuals with undetectable AMH and inhibin B, one of whom also had non‐(pre)malignant germ cells. Of the other 18, in whom AMH and/or inhibin B were detectable, only one had no germ cells.ConclusionsUndetectable serum AMH and inhibin B cannot reliably predict the absence of germ cells and germ cell tumours in individuals with 45,X/46,XY or 46,XY gonadal dysgenesis. This information should help in counselling about prophylactic gonadectomy, taking into account both the germ cell cancer risk and potential for gonadal function.

Tumour occurrence in women with Turner syndrome: A narrative review and single‐centre case series

AbstractBackgroundPopulation studies suggest cancer morbidity may be different in Turner syndrome (TS) compared to the background female population. However, significant variability is observed in cancer associations likely due to heterogeneity in patient cohorts. We explored the prevalence and patterns of cancer amongst a cohort of women with TS attending a dedicated TS clinic.MethodsRetrospective analysis of the patient database was performed to identify TS women who developed cancer. Population data (available before 2015) from the National Cancer Registration and Analysis Service database were used for comparison.ResultsOut of 156 TS women, median age of 32 (range 18–73) years, 9 (5.8%) had a recorded cancer diagnosis. Types of cancers were, bilateral gonadoblastoma, type 1 gastric neuroendocrine tumour (NET), appendiceal‐NET, gastrointestinal stromal tumour, plasma cell dyscrasia, synovial sarcoma, cervical cancer, medulloblastoma and aplastic anaemia. Median age at cancer diagnosis was 35 (range 7–58) years and two were detected incidentally. Five women had 45,X karyotype, three received growth hormone treatment and all except one received oestrogen replacement therapy. The cancer prevalence of the background age‐matched female population was 4.4%.ConclusionsWe confirm the previous observations that women with TS do not appear to be at overall increased risk of common malignancies. Our small cohort showed a spectrum of rare malignancies that are not typically associated with TS, except for a single patient with a gonadoblastoma. The slightly higher prevalence of cancer in our cohort might simply represent increased cancer prevalence in the background population, or might be related to small sample size and regular monitoring of these women due to TS per se.