Lactational Amenorrhea: Neuroendocrine Pathways Controlling Fertility and Bone Turnover.

Lactation is a physiological state of hyperprolactinemia and associated amenorrhea. Despite the fact that exact mechanisms standing behind the hypothalamus-pituitary-ovarian axis during lactation are still not clear, a general overview of events leading to amenorrhea may be suggested. Suckling remains the most important stimulus maintaining suppressive effect on ovaries after pregnancy. Breastfeeding is accompanied by high levels of prolactin, which remain higher than normal until the frequency and duration of daily suckling decreases and allows normal menstrual function resumption. Hyperprolactinemia induces the suppression of hypothalamic Kiss1 neurons that directly control the pulsatile release of GnRH. Disruption in the pulsatile manner of GnRH secretion results in a strongly decreased frequency of corresponding LH pulses. Inadequate LH secretion and lack of pre-ovulatory surge inhibit the progression of the follicular phase of a menstrual cycle and result in anovulation and amenorrhea. The main consequences of lactational amenorrhea are connected with fertility issues and increased bone turnover. Provided the fulfillment of all the established conditions of its use, the lactational amenorrhea method (LAM) efficiently protects against pregnancy. Because of its accessibility and lack of additional associated costs, LAM might be especially beneficial in low-income, developing countries, where modern contraception is hard to obtain. Breastfeeding alone is not equal to the LAM method, and therefore, it is not enough to successfully protect against conception. That is why LAM promotion should primarily focus on conditions under which its use is safe and effective. More studies on larger study groups should be conducted to determine and confirm the impact of behavioral factors, like suckling parameters, on the LAM efficacy. Lactational bone loss is a physiologic mechanism that enables providing a sufficient amount of calcium to the newborn. Despite the decline in bone mass during breastfeeding, it rebuilds after weaning and is not associated with a postmenopausal decrease in BMD and osteoporosis risk. Therefore, it should be a matter of concern only for lactating women with additional risk factors or with low BMD before pregnancy. The review summarizes the effect that breastfeeding exerts on the hypothalamus-pituitary axis as well as fertility and bone turnover aspects of lactational amenorrhea. We discuss the possibility of the use of lactation as contraception, along with this method's prevalence, efficacy, and influencing factors. We also review the literature on the topic of lactational bone loss: its mechanism, severity, and persistence throughout life.

Anti-Müllerian Hormone in Pathogenesis, Diagnostic and Treatment of PCOS.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women. It is characterized by chronic anovulation, hyperandrogenism, and the presence of polycystic ovary in ultrasound examination. PCOS is specified by an increased number of follicles at all growing stages, mainly seen in the preantral and small antral follicles and an increased serum level of Anti-Müllerian Hormone (AMH). Because of the strong correlation between circulating AMH levels and antral follicle count on ultrasound, Anti-Müllerian Hormone has been proposed as an alternative marker of ovulatory dysfunction in PCOS. However, the results from the current literature are not homogeneous, and the specific threshold of AMH in PCOS and PCOM is, therefore, very challenging. This review aims to update the current knowledge about AMH, the pathophysiology of AMH in the pathogenesis of PCOS, and the role of Anti-Müllerian Hormone in the treatment of this syndrome.

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.

Chronic Low Grade Inflammation in Pathogenesis of PCOS.

Polycystic ovary syndrome (PCOS) is a one of the most common endocrine disorders, with a prevalence rate of 5-10% in reproductive aged women. It's characterized by (1) chronic anovulation, (2) biochemical and/or clinical hyperandrogenism, and (3) polycystic ovarian morphology. PCOS has significant clinical implications and can lead to health problems related to the accumulation of adipose tissue, such as obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. There is also evidence that PCOS patients are at higher risk of cardiovascular diseases, atherosclerosis, and high blood pressure. Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation. According to known data, inflammatory markers or their gene markers are higher in PCOS patients. Correlations have been found between increased levels of C-reactive protein (CRP), interleukin 18 (IL-18), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), white blood cell count (WBC), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) in the PCOS women compared with age- and BMI-matched controls. Women with PCOS present also elevated levels of AGEs and increased RAGE (receptor for advanced glycation end products) expression. This chronic inflammatory state is aggravating by obesity and hyperinsulinemia. There are studies describing mutual impact of hyperinsulinemia and obesity, hyperandrogenism, and inflammatory state. Endothelial cell dysfunction may be also triggered by inflammatory cytokines. Many factors involved in oxidative stress, inflammation, and thrombosis were proposed as cardiovascular risk markers showing the endothelial cell damage in PCOS. Those markers include asymmetric dimethylarginine (ADMA), C-reactive protein (CRP), homocysteine, plasminogen activator inhibitor-I (PAI-I), PAI-I activity, vascular endothelial growth factor (VEGF) etc. It was also proposed that the uterine hyperinflammatory state in polycystic ovary syndrome may be responsible for significant pregnancy complications ranging from miscarriage to placental insufficiency. In this review, we discuss the most importance evidence concerning the role of the process of chronic inflammation in pathogenesis of PCOS.

Signs and symptoms, evaluation, and management of genitourinary tract consequences of premature ovarian insufficiency.

Premature ovarian insufficiency (POI) occurs in 1% of women under 40 years old. Hypoestrogenism associated with this condition may result in vaginal atrophy and urine incontinence, called genitourinary syndrome. The symptoms include: vaginal dryness, irritation, dyspareunia, and dysuria. There is relative lack of studies on the occurrence and treatment of genitourinary problems in women with POI. Prevalence rates vary from 17 to 54% depending on cause, duration of oestrogen depletion, and the treatment used. Patients with POI gain lower scores in tests measuring vaginal health or sexual function in comparison to healthy peers. Hormonal treatment in premature ovarian insufficiency is recommended until the natural age of menopause. The vaginal route of oestrogen administration is supposed to be the criterion standard in treating genitourinary symptoms. Androgen supplementation is not routinely recommended.

Spontaneous pregnancy in a patient with premature ovarian insufficiency - case report.

Diagnosis of premature ovarian insufficiency is usually sudden and distressful for the patient in terms of facing infertility. However, some patients with POI have intermittent ovarian activity with an overall 5% probability of pregnancy. We report the case of 27-year-old woman with premature ovarian insufficiency treated with hormone replacement therapy, who six months after diagnosis conceived spontaneously. Apart from bleeding episodes in the first trimester, the pregnancy course was uneventful, and a healthy neonate was delivered. Women with premature ovarian insufficiency should be informed about the small but nonetheless real possibility of pregnancy.

Premature ovarian insufficiency - hormone replacement therapy and management of long-term consequences.

Premature ovarian insufficiency (POI) correlates with increased risk of cardiovascular diseases, osteoporosis, genitourinary syndrome, and other symptoms of prolonged oestrogen deprivation. Properly selected therapy improves the quality of women's lives and reduces the risk of mortality. There is a wide spectrum of available oestrogen and progestogen formulations restoring proper levels of serum sex steroid hormones. The treatment should be implemented at recognition of the POI and continued to at least the age of natural menopause. Transdermal oestradiol and oral or vaginal progesterone administration provide the most physiological sex steroid replacement therapy. Patients' views and individual preference according the route, dose, and regimen of hormonal treatment have to be taken into consideration in order to achieve high compliance rates. Women with POI should be managed by a multidisciplinary team, such as a gynaecologist, endocrinologist, dietitian, and psychologist.

Insulin resistance indexes in women with premature ovarian insufficiency - a pilot study.

OBJECTIVES: Premature ovarian insufficiency (POI) is associated with hypoestrogenism and an increased risk of metabolic disorders. In many clinics, a variety of insulin resistance (IR) tests are used during routine clinical assessments. To date, there is no clear opinion about which of these tests should be applied in women with premature ovarian insufficiency (POI). Therefore, our preliminarily aim was to compare the most frequently used insulin resistance indexes in the clinical assessment of a group of POI women and a control group. MATERIAL AND METHODS: Our retrospective study included 98 women with karyotypically normal spontaneous POI aged 18-39 years and a control group of 78 healthy women. Each patient was given an oral glucose tolerance test (OGTT) to evaluate their insulin release and insulin resistance. In addition, each woman's insulin resistance (IR) was evaluated us-ing the homeostasis model assessment for insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index (QUICKI), the fasting glucose-to-insulin ratio (FGIR), and Matsuda and McAuley indexes. The two groups' glucose levels were compared at 0, 60 and 120 min of the OGTT. RESULTS: At 0 and 60 min of the OGTT, the insulin levels of the POI women were significantly higher than those of the control group. The number of women in whom IR was detected using the various kits was comparable between the two groups. CONLUSIONS: In conclusion, only the OGTT evaluation revealed a significant difference in insulin concentrations between the two study groups. The indexes most commonly used to detect IR did not detect differences in IR between the POI women and the members of the healthy control group. QUICKI detected significantly more women with IR within both study groups than other tests did.