Depression among women with cervical cancer: a systematic review and meta-analysis of available evidence.

A functional reproductive system relies on proper endocrine, metabolic, and immune factors. In humans, dysfunction in reproductive systems or disruption of natural processes may result in reproductive disorders including premature ovarian failure, Polycystic Ovary Syndrome (PCOS), and endometriosis. Premature ovarian insufficiency (POI) or premature menopause is an emerging public health concern, with a reported prevalence of 1–5.5%. A study in the Iranian population reported that 3.5% of women experienced POI. Clinically, POI is defined as the loss of ovarian activity before the age of 40, occurring approximately a decade before natural menopause, which typically happens at an average age of 50 to 53 years. It is characterized by amenorrhea, elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and reduced estradiol levels. The diagnosis of POI is a serious event for a woman, as it is a condition with medical, psychological, and reproductive implications, including increased risks of mortality, cardiovascular disorders, hypertension, type 2 diabetes, bone fractures and neuropsychological conditions. It also significantly impacts family planning, especially as women increasingly delay childbearing. POI may be idiopathic or associated with autoimmune and genetic abnormalities, infections, chemotherapy, radiotherapy, surgery, and certain medications. Modifiable lifestyle and environmental factors may also influence the risk of POI. The association between body mass index (BMI) and menopause remains controversial, with some studies reporting earlier menopause in both higher and lower BMI, while others show no association. Adipose tissue serves as an energy reservoir and is also the largest endocrine organ, secreting hormones known as adipokines. Dysfunction or abnormal levels of adipokines, due to underweight or obesity may contribute to reproductive disorders. As a multifaceted adipokine, Chemerin, also referred to as tazarotene-induced gene 2 (TIG-2) or retinoic acid receptor responder 2 (RARRES2), is a multifaceted adipokine expressed in various organs, including white adipose tissue and the ovaries. It binds to three receptors—chemokine-like receptor1 (CMKLR1), G-protein-coupled receptor 1(GPR1) and C–C motif chemokine receptor-like 2 (CCRL2)—to mediate diverse functions and signaling pathways. Chemerin is involved in inflammation, adipogenesis, metabolism, angiogenesis, and insulin secretion in adipose cells and is associated with conditions such as obesity, diabetes, and cancer. On the other hand, Chemerin and its receptors are expressed in the ovary and have a functional role, reduces steroidogenesis and cholesterol synthesis after IGF-1 or FSH stimulation by decreasing the levels of several proteins, including P450 and MAPK phosphorylation ERK1/2. In addition, chemerin regulates prohibitin expression, inhibiting FSH-induced steroidogenesis through suppression of the PI3K/Akt pathway and also downregulation of cyp19, NR5a 1/2. Chemerin also lowers aromatase expression, a key enzyme in sex hormone metabolism that catalyzes the conversion of androgens to estrogens in adipose tissue and ovarian granulosa cells and granulosa cell proliferation by reducing IGF-1R signaling pathways. In addition, Chemerin has been shown to inhibit the FSH receptor activity. These mechanisms are consistent with the hormonal alterations observed in POI. In particular, the decline in estrogen and androgens has been associated with metabolic dysregulation, contributing to the development of metabolic syndrome and an increased risk of cardiovascular disease. These biological and metabolic alterations may highlight the potential role of metabolic disturbances in the pathophysiology of POI. The Chemerin system is implicated in normal reproduction and reproductive disorders such as PCOS and gynecological cancer, but its role in women with POI remains unexplored. This study aimed to investigate the association between serum Chemerin levels, follicle-stimulating hormone, lipid profiles, and cardiometabolic indices with the POI in Iranian women. This case control study screened 535 women under 40 years old from medical centers affiliated with Kermanshah University of Medical Sciences (January 2023-May 2025). POI cases had prior specialist diagnosis; menstrual disturbance ≥ 4 months was confirmed, and a single basal FSH value (interpreted using a 25 IU/L cut-off) was measured at sampling. Exclusion criteria included conditions known to affect menstruation; genetically confirmed disorders associated with POI-related symptoms; and previous surgeries that could alter menstrual function. Participants were also excluded if they had acute or chronic diseases—such as renal or hepatic failure, autoimmune disorders, cardiovascular disease, cancer, uncontrolled hypertension, dyslipidemia, or diabetes—or if they were following prescribed diets, taking medications or nutritional supplements within the previous three mon