The impact of water pollution on the health of older people.

Water pollution exerts a negative impact on the health of both women and men, inducing hormonal changes, accelerating aging, and consequently leading to the premature onset of age-related health problems. Water pollutants can in general be classified as chemical (both organic and inorganic), physical, and biological agents. Certain chemical pollutants have been found to disrupt hormonal balance by blocking, mimicking, or disrupting functions within the intricate homeostasis of the human body. Moreover, certain water pollutants, including specific pesticides and industrial chemicals, have been associated with neurological and psychiatric disorders, such as mood swings, depression, cognitive decline, and anxiety, impacting both women and men. Water pollution is also associated with physical ailments, such as diarrhea, skin diseases, malnutrition, and cancer. Exposure to specific pollutants may promote premature menopause and vasomotor symptoms, elevate the risk of cardiovascular disease, and reduce bone density. In men, exposure to water pollution has been shown to reduce LH, FSH, and testosterone serum levels. The oxidative stress induced by pollutants prompts apoptosis of Sertoli and germ cells, inhibiting spermatogenesis and altering the normal morphology and concentration of sperm. Environmental estrogens further contribute to reduced sperm counts, reproductive system disruptions, and the feminization of male traits. Studies affirm that men generally exhibit a lower susceptibility than women to hormonal changes and health issues attributed to water pollutants. This discrepancy may be attributed to the varied water-related activities which have traditionally been undertaken by women, as well as differences in immune responses between genders. The implementation of effective measures to control water pollution and interventions aimed at safeguarding and enhancing the well-being of the aging population is imperative. The improvement of drinking water quality has emerged as a potential public health effort with the capacity to curtail the onset of cognitive impairment and dementia in an aging population.

Neuroendocrine disturbances in women with functional hypothalamic amenorrhea: an update and future directions.

Functional hypothalamic amenorrhea (FHA) is one of the most common causes of both primary and secondary amenorrhea in women of reproductive age. It is characterized by chronic anovulation and the absence of menses that appear as a result of stressors such as eating disorders, excessive exercise, or psychological distress. FHA is presumed to be a functional disruption in the pulsatile secretion of hypothalamic gonadotropin-releasing hormone, which in turn impairs the release of gonadotropin. Hypoestrogenism is observed due to the absence of ovarian follicle recruitment. Numerous neurotransmitters have been identified which play an important role in the regulation of the hypothalamic-pituitary-ovarian axis and of which the impairment would contribute to developing FHA. In this review we summarize the most recent advances in the identification of contributing neuroendocrine disturbances and relevant contributors to the development of FHA.

Bones and Hormones: Interaction between Hormones of the Hypothalamus, Pituitary, Adipose Tissue and Bone.

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.

PCOS in Adolescents-Ongoing Riddles in Diagnosis and Treatment.

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.

Cognitive decline and dementia in women after menopause: Prevention strategies.

Worldwide, cognitive decline and dementia are becoming one of the biggest challenges for public health. The decline in cognition and the development of dementia may be caused by predisposing or trigger factors. There is no consensus over whether the drop in estrogen levels after menopause is a risk factor for cognitive decline and dementia. This article discusses the prevention of cognitive decline and dementia in women after menopause, both primary prevention (essentially pharmacological intervention) and secondary prevention (chiefly diet and weight reduction). Further study is required to clarify whether menopausal hormone therapy (MHT) has a role in dementia.

Neuroendocrine Determinants of Polycystic Ovary Syndrome.

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.

The Genetic Backdrop of Hypogonadotropic Hypogonadism.

The pituitary is an organ of dual provenance: the anterior lobe is epithelial in origin, whereas the posterior lobe derives from the neural ectoderm. The pituitary gland is a pivotal element of the axis regulating reproductive function in mammals. It collects signals from the hypothalamus, and by secreting gonadotropins (FSH and LH) it stimulates the ovary into cyclic activity resulting in a menstrual cycle and in ovulation. Pituitary organogenesis is comprised of three main stages controlled by different signaling molecules: first, the initiation of pituitary organogenesis and subsequent formation of Rathke's pouch; second, the migration of Rathke's pouch cells and their proliferation; and third, lineage determination and cellular differentiation. Any disruption of this sequence, e.g., gene mutation, can lead to numerous developmental disorders. Gene mutations contributing to disordered pituitary development can themselves be classified: mutations affecting transcriptional determinants of pituitary development, mutations related to gonadotropin deficiency, mutations concerning the beta subunit of FSH and LH, and mutations in the DAX-1 gene as a cause of adrenal hypoplasia and disturbed responsiveness of the pituitary to GnRH. All these mutations lead to disruption in the hypothalamic-pituitary-ovarian axis and contribute to the development of primary amenorrhea.

Menopause in women with schizophrenia, schizoaffective disorder and bipolar disorder.

The transition to menopause, usually occurring between the ages of 40 and 55, is a time when women are particularly vulnerable. When preexisting mental illness is present, symptoms are often amplified during this period. Moreover, women with mental illnesses experience menopausal symptoms similarly to healthy women. In this narrative review we summarize the current data regarding menopause in women with schizophrenia, schizoaffective disorder, and bipolar disorder, as well as current standards of management and care. The management of chronic disease in women suffering from severe mental illness is also considered.

Hyperthyroidism associated with struma ovarii - a case report and review of literature.

BACKGROUND: Hyperthyroidism is a state characterized by elevated serum level of thyroid hormones: thyroxine (T4) and triiodothyronine (T3). This is mainly related to the condition and functioning of the thyroid gland. In 60-80% of cases elevation of these hormones are caused by Grave's disease. Thyrotoxicosis is an extreme presentation of hyperthyroidism which can, in rare cases, be caused by excessive synthesis of thyroxine by tumor cells. Struma ovarii is a rare ovarian teratoma composed of thyroid tissue in more than 50%. OBJECTIVE AND METHOD: To present a case of a 30-year-old female patient with a past history of Grave's disease treated by strumectomy 7 years prior; now presenting for the assessment of secondary amenorrhea. Pelvic ultrasound revealed bilateral solid tumors on the left and right ovary, respectively measuring 5 cm and 6 cm in diameter. Her clinical presentation was suggestive of overt hyperthyroidism, and she presented with a significantly elevated CA-125 (152.7 U/mL). RESULTS: The patient subsequently underwent a bilateral oophorectomy in which both masses were excised and histopathological examination confirmed teratoma maturum cysticum. Struma ovarii was noted as a component of the left ovary teratoma. CONCLUSION: Establishing a proper diagnosis of hyperthyroidism and elucidating its origin is often challenging. Struma ovarii is a rare cause of hyperthyroidism but should always be considered in case of treatment resistant hyperthyroidism. This case-report lends itself as an example of the value in maintaining gynecological-endocrinological knowledge in the setting if clinical gynecology.

Autoimmune Diseases in Patients with Premature Ovarian Insufficiency-Our Current State of Knowledge.

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.

Hyperthecosis: an underestimated nontumorous cause of hyperandrogenism.

Hyperthecosis is defined as the presence of nests of luteinized theca cells in the ovarian stroma. Persistent testosterone released by ovarian theca cells is unmasked postmenopausally through the loss of granulosa cell-mediated aromatization of testosterone to estradiol. Ovarian hyperthecosis (OH) usually presents with symptoms of hyperandrogenism and is often described as a severe or extreme form of Polycystic Ovary Syndrome (PCOS). Serum testosterone levels in excess of 150 ng/dl (>5.2 nmol/l) are seen in affected patients and this threshold is used to confirm a diagnosis. Treatment of hyperthecosis is multi-faceted. It addresses the attendant hyperandrogenism (hirsutism and virilization) as well as metabolic complications such as obesity and insulin resistance. Ultimately, laparoscopic bilateral salpingo-oophorectomy is definitive treatment. This remains the treatment of choice in postmenopausal women whereas treatment using GnRH agonists may be used in women of reproductive age, especially younger women. Nevertheless, if serum testosterone remains elevated despite several months of therapy with a GnRH agonist, surgery is often required for biopsy sample collection and further definitive therapy. In order to mitigate the common clinical manifestations of hyperandrogenism, anti-androgen therapy (either cyproterone acetate or spironolactone) may be used to suppress the actions of testosterone on tissues. In patients with impaired glucose metabolism and insulin resistance, Metformin should also be considered as part of treatment. Combined, such a treatment regimen will often lead to decreased ovarian androgen secretion.

Impact of Hormonal Replacement Therapy on Bone Mineral Density in Premature Ovarian Insufficiency Patients.

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-ß-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.

Kisspeptin and LH pulsatility in patients with functional hypothalamic amenorrhea.

PURPOSE: Functional hypothalamic amenorrhea (FHA) occurs in response to exaggerated stressors with or without body weight loss. Various hormones, neurotransmitters, and neuromodulators are involved in the control of GnRH and kisspeptin is one of them. Our study aimed to evaluate the putative temporal coupling between kisspeptin and GnRH-induced LH pulsatile secretion. METHODS: In total, 71 patients with FHA were selected for this study. All patients undergo to a pulsatility study for LH and kisspeptin evaluation (120 min, sampling every 10 min), and to an endocrine evaluation for prolactin (PRL), estradiol (E2), androstenedione (A), 17-hydroxy-progesterone (17OHP), TSH, fT3, fT4, insulin, cortisol and testosterone (T), glucose, total cholesterol, triglycerides. RESULTS: Our data demonstrated kisspeptin and LH pulsatile secretions and that both hormones are co-secreted and temporally coupled at time 0 (p < 0.05). When patients were subdivided in hypo-LH (≤3 mIU/ml, n = 58) and normo-LH (>3 mIU/ml, n = 13), more insights were observed on the specific correlations of metabolic and hormone profiles with pulsatility indexes of LH and kisspeptin. CONCLUSIONS: Our study demonstrated the presence of a distinct kisspeptin episodic secretion in patients with FHA, and showed the temporally coupling of kisspeptin with LH secretory episodes thus supporting that though in amenorrhea, the reproductive axis is still relying on kisspeptin to drive GnRH discharge. In addition, correlations among hormonal data sustain the hypothesis that stress-induced compensatory events are the main direct and indirect promoters of the reproductive blockade in patients affected by FHA.

Ovarian steroid cell tumor as an example of severe hyperandrogenism in 45-year-old woman.

Approximately, 5% of ovarian tumors have hormonal activity. Steroid cell tumors (SCTs) represent about 0.1% of all ovarian tumors. They cause hyperandrogenism associated with typical virilization. In this case report, we present 45-year-old women with unmalignant ovarian SCT-producing androgens which cause severe virilization and secondary amenorrhea lasting two years. Transvaginal ultrasound, computed tomography of adrenal glands, magnetic resonance imaging of small pelvis, laboratory tests (including serum concentration of FSH, LH, testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEA-S), as well as ROMA index) were performed. During hormonal evaluation, elevated concentrations of serum T - on admission 1.72 ng/ml and one month later 3.75 ng/ml (normal range 0.08-0.82 ng/ml) and A - 24.90 ng/ml (normal range 0.40-3.40 ng/ml) were found. The ROMA index was within the normal range. Enlargement of the left ovary by solid mass 56 × 43 mm was found during ultrasound examination. Based on small pelvis MRI scan and hormonal finding, patient was qualified for laparotomy. During this procedure, the left salpingo-oophorectomy with removal of the tumor was performed. The histopathological examination identified SCT. During follow-up examination, one day after surgery, we found serum testosterone levels within normal ranges - 0.74 ng/ml (normal range 0.08-0.82 ng/ml). This case shows that hormone-producing ovarian tumors are rare but very important clinical causes of severe hyperandrogenism.

Novel Mutations Segregating with Complete Androgen Insensitivity Syndrome and their Molecular Characteristics.

We analyzed three cases of Complete Androgen Insensitivity Syndrome (CAIS) and report three hitherto undisclosed causes of the disease. RNA-Seq, Real-timePCR, Western immunoblotting, and immunohistochemistry were performed with the aim of characterizing the disease-causing variants. In case No.1, we have identified a novel androgen receptor (AR) mutation (c.840delT) within the first exon in the N-terminal transactivation domain. This thymine deletion resulted in a frameshift and thus introduced a premature stop codon at amino acid 282. In case No.2, we observed a nonsynonymous mutation in the ligand-binding domain (c.2491C>T). Case No.3 did not reveal AR mutation; however, we have found a heterozygous mutation in CYP11A1 gene, which has a role in steroid hormone biosynthesis. Comparative RNA-Seq analysis of CAIS and control revealed 4293 significantly deregulated genes. In patients with CAIS, we observed a significant increase in the expression levels of PLCXD3, TM4SF18, CFI, GPX8, and SFRP4, and a significant decrease in the expression of SPATA16, TSACC, TCP10L, and DPY19L2 genes (more than 10-fold, p < 0.05). Our findings will be helpful in molecular diagnostics of patients with CAIS, as well as the identified genes could be also potential biomarkers for the germ cells differentiation process.

New mutation causing androgen insensitivity syndrome - a case report and review of literature.

Androgen insensitivity syndrome (AIS) is a congenital disorder in which a defect in the androgen receptor (AR) gene leads to cellular resistance to androgens. Defects in the AR gene, located on the X chromosome, result in the development of a feminine phenotype in chromosomally male (46, XY) individuals. In this case report, we present a 44 years old patient with complete androgen insensitivity syndrome (CAIS) initially presenting with primary amenorrhea. The patient underwent a full clinical evaluation, revealing hypoplastic vagina and a lack of uterus and ovaries. Hormonal evaluation revealed markedly elevated testosterone, FSH, and LH serum concentrations. Diagnostic imaging, including pelvic MRI, confirmed the presence of two solid masses in the inguinal canals (right 26 × 13 mm, left 25 × 15 mm). The patient underwent genetic testing, revealing a 46 XY karyotype and an as of yet unprecedented androgen receptor mutation. The type of the mutation was a single-base exchange - the substitution from cytosine to thymine in chromosome X:66942710 position (referred to human reference genome GRCh37), which has resulted in an amino acid changes from leucine (CTT) to phenyloalanine (TTT) in ligand-binding domain.

Reproduction in premature ovarian insufficiency patients - from latest studies to therapeutic approach.

Normal function of the ovaries, which is responsible for the hormonal and reproductive processes, is one of the most important determinants of fertility. Premature ovarian insufficiency (POI) is defined as cessation of menstrual cycle, increased serum follicle-stimulating hormone (FSH) levels, and decrease serum oestradiol levels in women before the age of 40 years. POI concerns about 1% of women and is characterised by severely diminished fertility. For the POI patient, this is one of the most dramatic problems. It influences their psychological status and functioning in society. The chance for spontaneous conception is very limited and ranges from 4 to 8%. For contemporary medicine, infertility treatment in POI patients is a challenge. The problem is that there are no effective therapies to augment ovarian activity in POI patients. At present, oocyte donation is regarded as the only proven method in the treatment of infertility in POI patients. However, nowadays we can observe important progress in the development of fertility preservation methods. In the POI field it refers to cryopreservation of oocytes, embryos, and ovarian tissue. Additionally, new methods known as in vitro activation of dormant follicles and possible use of stem cells should be mentioned.

Bone health and evaluation of bone mineral density in patients with premature ovarian insufficiency.

Oestrogens exert an influence on skeletal homeostasis during growth and adulthood. Regulation of osteoclasts and osteoblasts generation and apoptosis and prolongation of the lifespan of osteocytes are some of their actions on bone metabolism. Premature ovarian insufficiency (POI) and associated loss of oestrogen action on osteoclasts leads to trabecular perforation and loss of connectivity. Lack of oestrogens acting on osteoblast progenitors also causes a decrease in critical bone mass. Postmenopausal hypoestrogenism is associated with an increase in the number of lymphocyte B-cells expressing nuclear factor κB ligand (RANKL) in the bone marrow and elevated expression of RANKL by B-cells. Increased concentration of RANKL stimulates activation of osteoclasts and leads to oestrogen deficiency-associated bone loss. It has been proven that women with POI have decreased bone mineral density (BMD) measured in lumbar spine and femoral neck. The loss of bone mass associated with oestrogen deficiency is greater in trabecular than in cortical bone, thus women with POI have a significant decrease in BMD, particularly in the lumbar spine vertebrae. Smoking cessation, weight-bearing, and muscle-strengthening exercises on most days of the week, avoidance of excessive alcohol intake, and adequate supplementation of calcium and vitamin D are the main lifestyle rules necessary to avoid decline in BMD. The most important component of decreased BMD treatment in POI patients is systemic hormonal replacement therapy (HRT). HRT should provide hormonal balance and should mimic normal ovarian function as much as possible.

Consequences of premature ovarian insufficiency on women's sexual health.

Premature ovarian insufficiency (POI) is defined by amenorrhoea and decreased serum levels of oestrogens associated with increased serum gonadotropins concentrations before the age of 40 years. Patients suffering from POI present with irregular menses, either secondary or (less common) primary amenorrhoea, and subfertility. POI affects approximately 1 in 100 women by the age 40 years and 0.1% by 30 years of age. Both spontaneous and iatrogenic causes may induce POI, although up to 90% of POI cases are idiopathic. Impairment of sexual function is a common problem affecting women suffering from POI. Premature loss of gonadal function is particularly traumatic in young women and affects many aspects of physical and social life. POI patients suffer from genital pain due to vaginal dryness and diminished sexual arousal. Additionally, POI patients report increased anxiety, depressed mood, and have impaired interactions with their peers, which leads to feeling less feminine and having decreased self-esteem. Moreover, they have significantly decreased physical and psychological well-being when compared to age-matched controls. Systemic hormonal replacement therapy and topical oestrogen therapy as well as vaginal moisturisers may be used in the treatment of POI patients' sexual impairment.