Premature ovarian insufficiency (POI), previously known as premature ovarian failure or premature menopause, is defined as loss of ovarian function before the age of 40 years. The risk of POI before the age of 40 is 1%. Clinical symptoms develop as a result of estrogen deficiency and may include amenorrhea, oligomenorrhea, vasomotor instability (hot flushes, night sweats), sleep disturbances, vulvovaginal atrophy, altered urinary frequency, dyspareunia, low libido, and lack of energy. Most causes of POI remain undefined, however, it is estimated that anywhere from 4–30% of cases are autoimmune in origin. As the ovaries are a common target for autoimmune attacks, an autoimmune etiology of POI should always be considered, especially in the presence of anti-oocyte antibodies (AOAs), autoimmune diseases, or lymphocytic oophoritis in biopsy. POI can occur in isolation, but is often associated with other autoimmune conditions. Concordant thyroid disorders such as hypothyroidism, Hashimoto thyroiditis, and Grave’s disease are most commonly seen. Adrenal autoimmune disorders are the second most common disorders associated with POI. Among women with diabetes mellitus, POI develops in roughly 2.5%. Additionally, autoimmune-related POI can also present as part of autoimmune polyglandular syndrome (APS), a condition in which autoimmune activity causes specific endocrine organ damage. In its most common presentation (type-3), APS is associated with Hashomoto’s type thyroid antibodies and has a prevalence of 10–40%. 21OH-Antibodies in Addison’s disease (AD) can develop in association to APS-2.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age. This condition is characterized by hyperandrogenism and either oligo- or anovulation. PCOS patients often present comorbidities such as obesity, insulin resistance, impaired glucose metabolism, dyslipidemia, hypertension, metabolic syndrome, and an increased risk of diabetes. Given the profound implications of metabolic impairment in PCOS, the accurate diagnosis and management of these facets are imperative. The first-line approach to treatment involves lifestyle modifications, including dietary adjustments and exercise aimed at achieving weight loss, a strategy consistently emphasized across the literature. Supplementation with probiotics, vitamin D, and L-carnitine have also provided additional benefits to patients. In select cases, pharmacological interventions are needed for optimal therapeutic results. The most common medications used in PCOS include metformin, thiazolidinediones, inositols, and two classes of antidiabetic agents: dipeptidyl peptidase-IV (DPP-IV) inhibitors, and sodium–glucose cotransporter-2 (SGLT-2) inhibitors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new addition to the therapeutic arsenal for the metabolic management of PCOS. GLP-1 receptor agonists cause insulin release in a glucose-dependent manner, yielding clinical benefits such as heightened satiety, reduced appetite, and appetite regulation. GLP-1RAs have demonstrated efficacy in reducing glycated hemoglobin levels and promoting weight loss while ameliorating hyperlipidemia. Prior to initiating GLP-1RA therapy, patients should undergo screening for contraindications, including history of pancreatitis, diabetic retinopathy, or thyroid cancer. The effects of treatment should be monitored using laboratory testing and body weight measurements. Effective communication between clinician and patient should be maintained with regular check-in for a period of 6 to 12 months.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women and a major cause of anovulatory infertility. A diagnosis of PCOS is established based the presence of two out of three clinical symptoms, which are criteria accepted by the ESHRE/ASRM (European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine). Gonadotropin-releasing hormone (GnRH) is responsible for the release of luteinizing hormone, and follicle stimulating hormone from the pituitary and contributes a leading role in controlling reproductive function in humans. The goal of this review is to present the current knowledge on neuroendocrine determinations of PCOS. The role of such neurohormones as GnRH, and neuropeptides kisspeptin, neurokinin B, phoenixin-14, and galanin is discussed in this aspect. Additionally, different neurotransmitters (gamma-aminobutyric acid (GABA), glutamate, serotonin, dopamine, and acetylcholine) can also be involved in neuroendocrine etiopathogenesis of PCOS. Studies have shown a persistent rapid GnRH pulse frequency in women with PCOS present during the whole ovulatory cycle. Other studies have proved that patients with PCOS are characterized by higher serum kisspeptin levels. The observations of elevated serum kisspeptin levels in PCOS correspond with the hypothesis that overactivity in the kisspeptin system is responsible for hypothalamic-pituitary-gonadal axis overactivity. In turn, this causes menstrual disorders, hyperandrogenemia and hyperandrogenism. Moreover, abnormal regulation of Neurokinin B (NKB) is also suspected of contributing to PCOS development, while NKB antagonists are used in the treatment of PCOS leading to reduction in Luteinizing hormone (LH) concentration and total testosterone concentration. GnRH secretion is regulated not only by kisspeptin and neurokinin B, but also by other neurohormones, such as phoenixin-14, galanin, and Glucagon-like peptide-1 (GLP-1), that have favorable effects in counteracting the progress of PCOS. A similar process is associated with the neurotransmitters such as GABA, glutamate, serotonin, dopamine, and acetylcholine, as well as the opioid system, which may interfere with secretion of GnRH, and therefore, influence the development and severity of symptoms in PCOS patients. Additional studies are required to explain entire, real mechanisms responsible for PCOS neuroendocrine background.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. A diagnosis of PCOS is established when a patient exhibits two of three Rotterdam criteria: oligoovulation or anovulation, excess androgen activity, and polycystic ovarian morphology. The pathogenesis of PCOS, as it affects adolescents, is often discussed in terms of a “two-hit” theory. This refers to a stepwise process in which the first “hit” is an inborn congenitally programmed predisposition, while the second “hit” arises from a provocative factor such as insulin resistance. The dynamic physiological and anatomical changes which occur in puberty make for a challenging diagnosis in this group of patients. It is important to be mindful of the physiological particularities in adolescence which often mimic the symptoms of PCOS. In their first-year post-menarche, approximately 75% of menstruating adolescents report their cycle to last between 21–45 days. Recent studies have shown that regular menstrual cyclicity is only achieved within 2–3 years post-menarche. Anovulation, as a crucial diagnostic element for PCOS, features in about half of early-post-menarchal adolescents. Hirsutism and acne are the most common clinical manifestations of hyperandrogenism, and mild features are developed by most adolescents as a result of elevated androgen levels. Distinguishing between a pathological sign and normal features of maturation is often difficult. A polycystic ovarian morphology (PCOM) through ultrasound has been found in up to 40%, 35%, and 33.3% of patients when assessed at 2, 3, and 4 years, respectively, after menarche. PCOM in adolescence is not associated with future abnormalities in ovulatory rate or menstrual cycle duration. For this reason, international guidelines recommend against the use of pelvic ultrasound until 8 years post-menarche. The primary aim of management is focused mainly on improving hormonal and metabolic status, the prevention of future comorbid complications, and generally improving the overall quality of life in young women with PCOS. Considerable controversy surrounds the choice of optimal pharmacological treatment to address PCOS in adolescents. Reliable studies, which include this sub-section of the population, are very limited. There is a lack of robust and reliable trials in the literature addressing the use of combined oral contraceptives. Further work needs to be undertaken in order to provide safe and effective care to the adolescent population in this regard.

Premature ovarian insufficiency (POI) is hypogonadism associated with amenorrhea, increased levels of gonadotropins, and hypoestrogenism. Deficiency of estrogens may contribute to higher risk of cardiovascular diseases and death. POI patients present several risk factors for the development of cardiovascular diseases (CVD): endothelial dysfunction, abnormal lipid profile, insulin resistance, and insulin action disturbances. Therefore, patients present a higher risk of developing metabolic syndrome. Materials and methods: Follicle stimulating hormone (FSH), luteinizing hormone (LH), 17β-estradiol (E2), prolactin (PRL), testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), thyroid stimulating hormone (TSH), thyroxine (fT4), fasting serum glucose and insulin concentrations, homeostatic model for insulin resistance (HOMA-IR), and lipid profiles were assessed in 56 women (mean age: 30.7 ± 6.9) suffering from POI diagnosed according to European Society of Human Reproduction and Embryology (ESHRE) criteria and 68 healthy age-and-weight matched women (mean age: 27.3 ± 4.5). Results: After regression analysis with BMI and age correction, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) serum concentrations were found to be significantly higher in the POI group, when compared to healthy subjects, whilst triglycerides, glucose, insulin serum concentrations, HOMA-IR, as well as systolic (SBP) and diastolic blood pressure (DBP) did not differ significantly between both groups. A significant positive correlation was identified between TC and LDL-C levels, regardless of BMI and age, whilst SBP correlated only with serum glucose concentration. Additionally, FSH correlated positively with fasting serum glucose concentration after BMI and age correction. Conclusions: Certain metabolic parameters appeared to correlate with POI and these correlations persisted after correction for BMI and age. More research is required to determine the influence of absent ovulatory function on metabolic profiles in POI women. This information may additionally help in early identification of CVD risk factors in those patients.

Premature ovarian insufficiency is a reproductive endocrine disorder characterized by the cessation of ovarian function before the age of 40 years. Although the etiopathology of POI remains largely unknown, certain causative factors have been identified. Individuals affected by POI are at an increased risk of experiencing bone mineral density (BMD) loss. Hormonal replacement therapy (HRT) is recommended for patients with POI to mitigate the risk of decreased BMD, starting from the time of diagnosis until reaching the average age of natural menopause. Various studies have compared the dose-effect relationship of estradiol supplementation, as well as different HRT formulations on BMD. The impact of oral contraception on reduced BMD or the potential benefits of adding testosterone to estrogen replacement therapy are still subjects of ongoing discussion. This review provides an overview of the latest advancements in the diagnosis, evaluation, and treatment of POI as it relates to BMD loss.