Anovulation in reproductive years [keywords]
- [Polycystic ovary sindrome: impact on reproductive and material fetal health]. [English Abstract, Journal Article]
- Rev Fac Cien Med Univ Nac Cordoba 2016; 73(2):102-13.
Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism (H), oligo-anovulation (O) and / or polycystic ovaries (P). There is currently little information on perinatal complications.to investigate obstetric and neonatal characteristics of women with PCOS in our population.we studied 87 pregnant women with PCOS (categorized in four phenotypes according Rotterdam Consensus: A (H + O + P) n = 53; B (H + O) n = 9; C (H + P) n = 16 and D (O + P) n = 9) and 96 without PCOS (control). We analyzed clinical and biochemical features (age, anthropometry hirsutism, acanthosis nigricans, OGTT, insulin, lipid profile, androgen and gonadotropins) during preconception, (weight gain, blood pressure, OGTT) through gestation and occurrence of perinatal complications.we found no differences in age (29.4 ± 4 and 28.7 ± 5 years) and body mass index (28.2 ± 6 and 27.8 ± 6 kg / m2) in both groups; while patients with PCOS had higher waist circumference, blood pressure and acanthosis nigricans versus control. Despite similar weight gain, patients with PCOS had higher percentage of perinatal complications. In the A phenotype RR for perinatal adverse outcomes was 2.37 (95%CI: 1.67-3.36, p <0.001). The HOMA-IR index preconception and fasting glucose during pregnancy were the predictors for these complications (p=0.01).patients with PCOS have a higher risk for complications during pregnancy and newborns more frequently have low weight or macrosomy. A careful history can recognize patients with higher perinatal risk to develop complications.
- Evolutionary determinants of polycystic ovary syndrome: part 1. [Journal Article, Review]
- Fertil Steril 2016 Jul; 106(1):33-41.
Polycystic ovary syndrome (PCOS) is a common and complex genetic disorder that develops under varying degrees of hyperandrogenemic and hyperinsulinemic conditions that cause phenotypic variability ranging from mild hirsutism to anovulation and infertility. In addition to increased risk of reproductive disability, PCOS is associated with metabolic diseases including type 2 diabetes, dyslipidemia, and cardiovascular disease. Similar prevalence rates and shared genetic susceptibility of PCOS among different populations suggest that genetic risk factors were already present in the ancestors of humans. Contemporary human genetic studies inform us that the origin of human ancestors is from Africa. Sharing common susceptibility loci between Chinese and European ancestry suggests that PCOS may have persisted for more than 50,000 years, before the migration of humans out of Africa. Although PCOS is the most common cause of anovulatory infertility, its high prevalence is still a paradox. From an evolutionary perspective, the pathogenic mechanisms underlying PCOS might be candidate factors for survival advantage of the human being. Former compensatory advantageous factors may become pathogenic mechanisms underlying complex metabolic disease with prolonged life expectancy and transition to sedentary lifestyle.
- What affects functional ovarian reserve, thyroid function or thyroid autoimmunity? [Journal Article]
- Reprod Biol Endocrinol 2016; 14(1):26.
Thyroid dysfunction is the most common autoimmune endocrine disorder in women of reproductive age, and is associated with menstrual irregularities, anovulation and infertility. Whether it is thyroid function or thyroid autoimmunity that affects functional ovarian reserve (FOR, i.e., the small growing ovarian follicle pool) reflected in anti-Müllerian hormone (AMH) has, however, remained under dispute.We investigated in 225 infertile women whether thyroid function, after adjustment for thyroid autoimmunity, affects FOR within what is considered normal thyroid function (TSH, 0.4-4.5μIU/mL) by assessing AMH levels in reference to TSH levels, stratified for TSH < or ≥3.0μIU/mL. Thyroid autoimmunity was defined by presence of anti-thyroid peroxidase, -thyroglobulin and/or -thyroid receptor antibodies.Mean age of studied women was 38.4 ± 5.0 years; their mean AMH was 1.3 ± 2.0 ng/mL and mean TSH 1.8 ± 0.9 μIU/mL. Thyroid autoimmunity was present in 11.1 % of patients. Women with TSH <3.0μIU/mL presented with significantly higher AMH compared to those with TSH ≥3.0μIU/Ml (P = 0.03). This difference remained significant after adjustment for thyroid autoimmunity as well as age (P = 0.02).Even after adjustment for thyroid autoimmunity and age, TSH <3.0μIU/mL in euthyroid infertility patients is associated with significantly better FOR (higher AMH) than TSH ≥3.0μIU/mL. This observation suggests a direct beneficial effect of lower TSH levels on follicular recruitment, and warrants investigations of thyroxin supplementation in infertile women with TSH levels ≥3.0μIU/mL in attempts to improve FOR.
- Diagnostic criteria for PCOS: Is there a need for a rethink? [REVIEW, JOURNAL ARTICLE]
- Best Pract Res Clin Obstet Gynaecol 2016 Mar 31.
The diagnostic criteria for polycystic ovarian syndrome (PCOS) have been grouped in different classifications that have been conflicting for many years. At present, the classification of Rotterdam is the most used, but with varying frequency depending on the country and medical specialties. This classification is now >10 years old. Although its fundamental principle (two criteria required out of three) is still valid, each of its three items (oligo-anovulation (OA), hyperandrogenism (HA), and polycystic ovarian morphology (PCOM)) needs to be updated. The definition of biological HA is still unresolved. The criteria used to define OA are insufficient. The definition of PCOM proposed in 2003 is now obsolete when using the latest generation of ultrasound machines. The serum anti-Müllerian hormone (AMH) assay seems increasingly to be an excellent substitute for follicular count and is likely to emerge as the official PCOM marker. A new consensus conference is urgently needed.
- The role of anti-Müllerian hormone in the pathogenesis and pathophysiological characteristics of polycystic ovary syndrome. [Journal Article, Research Support, Non-U.S. Gov't, Review]
- Eur J Obstet Gynecol Reprod Biol 2016 Apr.:82-7.
Polycystic ovarian syndrome (PCOS) is one of the major causes of anovulatory infertility. High levels of anti-Müllerian hormone (AMH) in the serum of PCOS patients participate in the major steps of the anovulation, and are related to pathogenesis and pathophysiological characteristic of PCOS, including the interactions of AMH with intra/extra ovarian factors like FSH, LH, androgen, and estrogen, as well as the role of AMH in folliculogenesis of PCOS. AMH promotes follicular atresia which may participate in the follicle pattern in PCOS patients. Recent years, the abnormally increased AMH in serum and follicle fluid of PCOS patients have attracted many scholars' attention. In this review, we summarized the role of AMH played in PCOS patients. It is of great significance for clarifying the role of AMH in the diagnosis and treatment of PCOS patients because AMH has the potential to increase our understanding of ovarian pathophysiology and to guide the clinical management of a broader range of conditions.
- Prevalence of polycystic ovary syndrome and its associated complications in Iranian women: A meta-analysis. [Journal Article, Review]
- Iran J Reprod Med 2015 Oct; 13(10):591-604.
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and is the most common cause of infertility due to anovulation. There is no single criterion for the diagnosis of this syndrome.The purpose of this study was to investigate the prevalence of PCOS and its associated complications in Iranian women using meta-analysis method.Prevalence of PCOS was investigated from the SID, Goggle scholar, PubMed, Magiran, Irandoc, and Iranmedex, and weighting of each study was calculated according to sample size and prevalence of the binomial distribution. Data were analyzed using a random-effects model meta-analysis (Random effects model) and the software R and Stata Version 11.2.30 studies conducted between the years 2006 to 2011 were entered into meta-analysis. The total sample size was 19, 226 women aged between 10-45 years. The prevalence of PCOS based on National institute of child health and human disease of the U.S was, 6.8% (95 % CI: 4.11-8.5), based on Rotterdam was 19.5% (95 % CI: 2.24-8.14), and based on ultrasound was 4.41% (95% CI: 5.68-4.14). Also, the prevalence of hirsutism was estimated to be 13%, acne 26%, androgenic alopecia 9%, menstrual disorders 28%, overweight 21%, obesity 19%, and infertility 8%.The prevalence of PCOS in Iran is not high. However, given the risk of complications such as heart disease - cardiovascular and infertility, prevention of PCOS is important; we suggest that health officials must submit plans for the community in this respect.
- The Diagnosis of Polycystic Ovary Syndrome in Adolescents. [Journal Article, Research Support, N.I.H., Extramural, Review]
- Pediatrics 2015 Dec; 136(6):1154-65.
Consensus has recently been reached by international pediatric subspecialty societies that otherwise unexplained persistent hyperandrogenic anovulation using age- and stage-appropriate standards are appropriate diagnostic criteria for polycystic ovary syndrome (PCOS) in adolescents. The purpose of this review is to summarize these recommendations and discuss their basis and implications. Anovulation is indicated by abnormal uterine bleeding, which exists when menstrual cycle length is outside the normal range or bleeding is excessive: cycles outside 19 to 90 days are always abnormal, and most are 21 to 45 days even during the first postmenarcheal year. Continued menstrual abnormality in a hyperandrogenic adolescent for 1 year prognosticates at least 50% risk of persistence. Hyperandrogenism is best indicated by persistent elevation of serum testosterone above adult norms as determined in a reliable reference laboratory. Because hyperandrogenemia documentation can be problematic, moderate-severe hirsutism constitutes clinical evidence of hyperandrogenism. Moderate-severe inflammatory acne vulgaris unresponsive to topical treatment is an indication to test for hyperandrogenemia. Treatment of PCOS is symptom-directed. Cyclic estrogen-progestin oral contraceptives are ordinarily the preferred first-line medical treatment because they reliably improve both the menstrual abnormality and hyperandrogenism. First-line treatment of the comorbidities of obesity and insulin resistance is lifestyle modification with calorie restriction and increased exercise. Metformin in conjunction with behavior modification is indicated for glucose intolerance. Although persistence of hyperandrogenic anovulation for ≥2 years ensures the distinction of PCOS from physiologic anovulation, early workup is advisable to make a provisional diagnosis so that combined oral contraceptive treatment, which will mask diagnosis by suppressing hyperandrogenemia, is not unnecessarily delayed.
- AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME--PART 1. [Journal Article, Practice Guideline]
- Endocr Pract 2015 Nov; 21(11):1291-300.
Polycystic Ovary Syndrome (PCOS) is recognized as the most common endocrine disorder of reproductive-aged women around the world. This document, produced by the collaboration of the American Association of Clinical Endocrinologists (AACE) and the Androgen Excess and PCOS Society (AES) aims to highlight the most important clinical issues confronting physicians and their patients with PCOS. It is a summary of current best practices in 2015. PCOS has been defined using various criteria, including menstrual irregularity, hyperandrogenism, and polycystic ovary morphology (PCOM). General agreement exists among specialty society guidelines that the diagnosis of PCOS must be based on the presence of at least two of the following three criteria: chronic anovulation, hyperandrogenism (clinical or biological) and polycystic ovaries. There is need for careful clinical assessment of women's history, physical examination, and laboratory evaluation, emphasizing the accuracy and validity of the methodology used for both biochemical measurements and ovarian imaging. Free testosterone (T) levels are more sensitive than the measurement of total T for establishing the existence of androgen excess and should be ideally determined through equilibrium dialysis techniques. Value of measuring levels of androgens other than T in patients with PCOS is relatively low. New ultrasound machines allow diagnosis of PCOM in patients having at least 25 small follicles (2 to 9 mm) in the whole ovary. Ovarian size at 10 mL remains the threshold between normal and increased ovary size. Serum 17-hydroxyprogesterone and anti-Müllerian hormone are useful for determining a diagnosis of PCOS. Correct diagnosis of PCOS impacts on the likelihood of associated metabolic and cardiovascular risks and leads to appropriate intervention, depending upon the woman's age, reproductive status, and her own concerns. The management of women with PCOS should include reproductive function, as well as the care of hirsutism, alopecia, and acne. Cycle length >35 days suggests chronic anovulation, but cycle length slightly longer than normal (32 to 35 days) or slightly irregular (32 to 35-36 days) needs assessment for ovulatory dysfunction. Ovulatory dysfunction is associated with increased prevalence of endometrial hyperplasia and endometrial cancer, in addition to infertility. In PCOS, hirsutism develops gradually and intensifies with weight gain. In the neoplastic virilizing states, hirsutism is of rapid onset, usually associated with clitoromegaly and oligomenorrhea. Girls with severe acne or acne resistant to oral and topical agents, including isotretinoin (Accutane), may have a 40% likelihood of developing PCOS. Hair loss patterns are variable in women with hyperandrogenemia, typically the vertex, crown or diffuse pattern, whereas women with more severe hyperandrogenemia may see bitemporal hair loss and loss of the frontal hairline. Oral contraceptives (OCPs) can effectively lower androgens and block the effect of androgens via suppression of ovarian androgen production and by increasing sex hormone-binding globulin. Physiologic doses of dexamethasone or prednisone can directly lower adrenal androgen output. Anti-androgens can be used to block the effects of androgen in the pilosebaceous unit or in the hair follicle. Anti-androgen therapy works through competitive antagonism of the androgen receptor (spironolactone, cyproterone acetate, flutamide) or inhibition of 5α-reductase (finasteride) to prevent the conversion of T to its more potent form, 5α-dihydrotestosterone. The choice of antiandrogen therapy is guided by symptoms. The diagnosis of PCOS in adolescents is particularly challenging given significant age and developmental issues in this group. Management of infertility in women with PCOS requires an understanding of the pathophysiology of anovulation as well as currently available treatments. Many features of PCOS, including acne, menstrual irregularities, and hyperinsulinemia, are common in normal puberty. Menstrual irregularities with anovulatory cycles and varied cycle length are common due to the immaturity of the hypothalamic-pituitary-ovarian axis in the 2- to 3-year time period post-menarche. Persistent oligomenorrhea 2 to 3 years beyond menarche predicts ongoing menstrual irregularities and greater likelihood of underlying ovarian or adrenal dysfunction. In adolescent girls, large, multicystic ovaries are a common finding, so ultrasound is not a first-line investigation in women <17 years of age. Ovarian dysfunction in adolescents should be based on oligomenorrhea and/or biochemical evidence of oligo/anovulation, but there are major limitations to the sensitivity of T assays in ranges applicable to young girls. Metformin is commonly used in young girls and adolescents with PCOS as first-line monotherapy or in combination with OCPs and anti-androgen medications. In lean adolescent girls, a dose as low as 850 mg daily may be effective at reducing PCOS symptoms; in overweight and obese adolescents, dose escalation to 1.5 to 2.5 g daily is likely required. Anti-androgen therapy in adolescents could affect bone mass, although available short-term data suggest no effect on bone loss.
- Polycystic ovary syndrome (PCOS) and hyperandrogenism: the role of a new natural association. [Journal Article]
- Minerva Ginecol 2015 Oct; 67(5):457-63.
Polycystic ovary syndrome (PCOS) affects 5-10% of women of childbearing age and manifests itself through oligomenorrhea, anovulation, hirsutism, micro-polycystic ovaries. Insulin resistance is a characteristic of PCOS patients and is more pronounced in obese patients. Insulin resistance and consequent hyperinsulinemia are related to many aspects of the syndrome such as hyperandrogenism, reproductive disorders, acne and hirsutism. In the long-term it may increase the risk of cardiovascular disease and negatively affect lipid profile and blood pressure. Changes in lifestyle and diet can partially improve these aspects. The use of insulin-sensitizing drugs such as metformin often normalises the menstrual cycle, improving hyperandrogenism and, subsequently, the response to ovulation induction therapies. New molecules have recently been marketed, that produce the same results, but without the side-effects. One of these is myo-inositol, a new insulin-sensitizing molecule which has been successfully administered to women suffering from PCOS. Associations between inositol and other compounds that can increase the therapeutic effect have been proposed. Of these, we found to be interesting the association with monacolin K, a natural statin that reduces cholesterol levels starting point of the synthesis of steroids, including androgens, and lipoic acid, known for its anti-inflammatory, antioxidant and insulin-sensitizing activity. We decided to assess the efficacy of the product.We recruited 30 women aged between 24 and 32 years suffering from PCOS with insulin resistance, HOMA index>2.5 and no other endocrine diseases. The following were assessed: Body Mass Index (BMI), characteristics of menstrual cycles, lipid profile (total cholesterol, and HDL), androgens (total testosterone and androstenedione). The patients were also assessed for the degree of hirsutism using the Ferriman-Gallwey Score>8. The subjects were divided into two groups: Group A, treated with an association of 1 g myo-inositol, 5 mg monacolin K and 400 mg lipoic acid for 6 months; Group B, treated with a double dosage of 2 g myo-inositol, 10 mg monacolin K, 800 mg lipoic acid for 6 months.The results have shown good efficacy of both dosages, although women treated with a double dosage of myo-inositol, monacolin K and lipoic acid showed a significantly greater improvement in terms of lipid parameters and those connected with hyperandrogenism.This new myo-inositol, monacolin K and lipoic acid association contains appropriate substances to contrast various etiopathogenic elements responsible for the onset of PCOS and the symptoms of hyperandrogenism and dyslipidemia related to it.
- Obesity and fertility. [Journal Article]
- Horm Mol Biol Clin Investig 2015 Oct; 24(1):5-10.
The prevalence of overweight and obesity in women of reproductive age has increased over the past 30 years. Infertility affects 1 in 7 couples, and female obesity is associated with anovulation. The mechanisms by which excessive fat delays time to pregnancy (TTP) appear rooted in ovulatory problems and direct effects on oocytes, causing poorer embryo development, as well as in effects on the endometrium. Weight loss in women has been shown to improve conception, but not necessarily live birth rates following fertility treatment, and further research in this area is needed. The obesity epidemic has been accompanied by a potential rise in male infertility, which has been attributed to hormonal disturbances and compromised semen parameters.