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 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.

The bony skeleton, as a structural foundation for the human body, is essential in providing mechanical function and movement. The human skeleton is a highly specialized and dynamic organ that undergoes continuous remodeling as it adapts to the demands of its environment. Advances in research over the last decade have shone light on the various hormones that influence this process, modulating the metabolism and structural integrity of bone. More recently, novel and non-traditional functions of hypothalamic, pituitary, and adipose hormones and their effects on bone homeostasis have been proposed. This review highlights recent work on physiological bone remodeling and discusses our knowledge, as it currently stands, on the systemic interplay of factors regulating this interaction. In this review, we provide a summary of the literature on the relationship between bone physiology and hormones including kisspeptin, neuropeptide Y, follicle-stimulating hormone (FSH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), growth hormone (GH), leptin, and adiponectin. The discovery and understanding of this new functionality unveils an entirely new layer of physiologic circuitry.

Premature ovarian insufficiency (POI) is a type of hypergonadotropic hypogonadism caused by impaired ovarian function before the age of 40. Due to the hypoestrogenism, women with POI experience a variety of health complications, including an increased risk of bone mineral density loss and developing osteopenia and osteoporosis, which poses an important problem for public health. Purpose: The aim of this study was to evaluate and compare the values of bone mineral density (BMD), T-score and Z-score within the lumbar spine (L1-L4) using the dual energy X-ray absorptiometry method. The dual-energy X-ray absorptiometry (DXA) scans described in this original prospective article were performed at the time of POI diagnosis and after treatment with sequential hormone replacement therapy (HRT). Materials and methods: This study included 132 patients with a mean age of 31.86 ± 7.75 years who had been diagnosed with idiopathic POI. The control group consisted of 17 healthy women with regular menstrual cycles, with a mean age of 23.21 ± 5.86 years. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17-estradiol (E2), prolactin (PRL), testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), thyroid-stimulating hormone (TSH), free thyroxine (fT4), insulin, and fasting serum glucose were measured. Lumbar spine (L1-L4) BMD was assessed by means of dual-energy X-ray absorptiometry. DXA scans were performed at the time of diagnosis and following treatment with sequential hormone replacement therapy (HRT) comprised of daily oral 2 mg 17-β-estradiol and 10 mg dydrogesterone. The mean time of observation was 3 ± 2 years. Results: Patients in the POI group presented with characteristic hypergonadotropic hypogonadism. They had a significantly decreased mean lumbar spine BMD when compared to healthy controls (1.088 ± 0.14 g/cm²) vs. 1.150 ± 0.30 g/cm²) (p = 0.04) as well as a decreased T-score (0.75 ± 1.167 vs. −0.144 ± 0.82) (p = 003). There was a significant increase in BMD (1.088 ± 0.14 vs. 1.109 ± 0.14; p < 0.001), T-score (−0.75 ± 1.17 vs. −0.59 ± 1.22; p < 0.001), and Z-score (−0.75 ± 1.12 vs. −0.49 ± 1.11; p < 0.001) after the implementation of HRT when compared to pre-treatment results. Conclusions: In conclusion, this study has demonstrated that patients with POI often have decreased bone mineral density and that the implementation of HRT has a significant and positive influence on bone mass. The implementation of full-dose HRT and monitoring of bone status is particularly important in these patients.

KNDy (kisspeptine, neurokinin B, dynorphin) neurons, located in the hypothalamus, play a crucial role in the development of vasomotor symptoms (VSM) in menopausal women. Estrogen withdrawal during menopause leads to the hyperactivation of kisspeptin and neurokinin B (NKB) secretion, contributing to the onset of these symptoms. The identification of NKB/neurokinin B receptor (NK3R) signaling as a key mechanism in menopausal hot flashes has driven the development of NK3R antagonists. These antagonists restore the disrupted balance in KNDy neuron activity caused by estrogen deficiency, thereby reducing the frequency and severity of VMS. In 2023, the FDA approved fezolinetant, the first selective NK3R antagonist, for the treatment of moderate to severe VMS associated with menopause. Additionally, elinzanetant, a dual neurokinin-1 and neurokinin-3 receptor antagonist, has demonstrated promising results. The approval application for elinzanetant was supported by positive findings from the OASIS 1, 2, and 3 Phase III clinical studies. The dual antagonism of NK-1 and NK-3 receptors enhances its efficacy by alleviating menopause-related sleep disturbances and modulating peripheral vasodilatation. In this regard, elinzanetant represents a promising non-hormonal treatment that targets the underlying causes of VMS through NK-1 and NK-3 receptor pathways. The development of neurokinin B antagonist for VMS treatment exemplifies the impact of advanced pharmacological research on gynecological endocrinology.