Claudio Villarroel

Elevated anti-Müllerian hormone (AMH) and inhibin B levels in prepubertal girls with type 1 diabetes mellitus

Objective  Elevated anti‐Müllerian hormone (AMH) and adrenal androgen levels have been observed during childhood in girls at risk of developing polycystic ovarian syndrome (PCOS). The aim of this study was to evaluate ovarian function and adrenal steroid levels in prepubertal girls with type 1 diabetes mellitus (T1D).

Hirsutism and oligomenorrhea are appropriate screening criteria for polycystic ovary syndrome in adolescents

Abstract We evaluated the association of hirsutism and oligomenorrhea (persistent menstrual cycles > 45 days) as screening criteria for the detection of biochemical hyperandrogenism (BH) and polycystic ovaries (PCOM) during adolescence and determined which androgens, granulosa cell hormone, ultrasonographic parameters have the best association with polycystic ovary syndrome (PCOS). Hirsute girls with oligomenorrhea (N = 26 Hirs/Oligo group) and non-hirsute girls with regular cycles (N = 63, C group) were studied. Prevalence of BH and PCOM, diagnostic performance of androgens and ultrasound parameters for PCOS diagnosis were analyzed. BH and PCOM prevalence were higher in the Hirs/Oligo girls than in the C girls (76.9% versus 25.5%; 92.3% versus 33.3%, respectively; p < 0.0001). A complete PCOS phenotype (Hirs/Oligo with BH and PCOM) was observed in 73.1% of the Hirs/Oligo group. The presence of both BH and PCOM was observed in 7.9% of the C group. The parameters with the best diagnostic performance were free androgen index ≥6.1, testosterone ≥2.4 nmol/L, follicle number ≥12 and ovarian volume ≥10 ml anti-Müllerian hormone (AMH) exhibited a low diagnostic accuracy. Hirsutism and persistent menstrual cycle over 45 days are highly associated with BH and PCOM suggesting that the presences of both criteria are necessary for the diagnosis of PCOS during adolescence. Chinese abstract 我们评估多毛合并月经稀发（持续的月经周期超过45天）作为生化高雄激素（BH）和青春期多囊卵巢（PCOM）筛选标准的情况，并确定雄激素，颗粒细胞激素，超声参数中哪个与多囊卵巢综合征（PCOS）联系最为密切。本文研究了多毛合并月经稀发的女孩（N=26 多毛/月经稀发组）和非多毛并且月经规律女孩（N=63 C组）BH和PCOM的患病率，并分析了雄性激素和超声参数对PCOS的诊断性作用。BH和PCOM在多毛/月经稀发女孩组的患病率高于C 组女孩（分别是76.9%和25.5%；92.3%和33.3%；P＜0.0001）。73.1%的多毛/月经稀发组患者呈现了一个完整的PCOS表型（多毛/月经稀发合并BH和PCOM）。仅有7.9%的C组患者出现了BH和PCOM。最好的诊断性参数是游离雄激素指数≥6.1，睾酮≥2.4 nmol/L，卵泡数≥12和卵巢体积≥10ml,而抗苗勒管激素（AMH）诊断准确性低。多毛和持续性月经周期超过45天与BH和PCOM高度相关表明了这两个标准在诊断青春期PCOS中是必要的。

Assessment of diagnostic competence of plasmatic androgens on polycystic ovary syndrome based on receiver operator characteristic curves

Objective. This study was designed to assess the diagnostic potency of different androgens in hyperandrogenaemia criterion on polycystic ovary syndrome (PCOS) based on receiver operator characteristic (ROC) curves analysis. Methods. We evaluated 55 PCOS patients and 27 healthy fertile women (control). Androgen evaluation included bio-available testosterone (BAT) by ammonium sulphate precipitation, Free Testosterone Index (FTI), androstenedione (A), total testosterone and dehydroepiandrosterone sulphate (DHEA-S). Results. The androgen tests with the best diagnostic capacities were FTI and BAT. Although T and A had similar diagnostic potencies, A detected 5% of PCOS patients that could not be recognised by FTI, BAT (%), or T. The association of FTI, BAT (%) and A identified 96.36% of the hyperandrogenaemic patients. DHEA-S showed a wide dispersion of values and therefore poor discriminatory competence. Discussion. This study suggests that routine androgen evaluation in PCOS should include FTI, BAT and A to avoid misdiagnosis. ROC curve analysis of these tests on patients with the complete spectrum of PCOS phenotypes is needed to confirm these results.

Transient expression of progesterone receptor and cathepsin-l in human granulosa cells during the periovulatory period

OBJECTIVE To study in vivo the progesterone receptor (PR) expression levels in human granulosa cells (GCs) during the periovulatory period and the affect of the protein kinase A (PKA) pathway on PR expression and cathepsin-L expression-activation. DESIGN Experimental study. SETTING University research unit. PATIENT(S) Twenty-five women of reproductive age. INTERVENTION(S) Follicular fluid and GCs obtained from spontaneous cycles before and during the normal luteinizing hormone surge, and samples obtained 36 hours after human chorionic gonadotropin (hCG) administration in patients undergoing in vitro fertilization. MAIN OUTCOME MEASURE(S) To determine PR, cathepsin-L messenger RNA (mRNA) analysis via real-time polymerase chain reaction, and protein of PR, cathepsin-L, and PKA in human GCs. RESULT(S) The Western blot analysis revealed that bands of PR (isoform A) were the most abundant and that mRNA (PR-A and PR-B) have a temporal pattern of expression throughout the periovulatory period. The protein levels of PR and cathepsin-L were up-regulated by hCG. The abundance of PR was diminished in the presence of PKA inhibitor, and cathepsin-L with PR receptor antagonist. CONCLUSION(S) The transient expression of PR in human GCs of the preovulatory follicle suggests that PR and its ligand play a role in the activation of cathepsin-L, which is presumably involved in the degradation of the follicular extracellular matrix during human ovulation.

Ovarian function in adolescents with McCune-Albright syndrome.

Abstract Objective: To evaluate ovarian function, especially ovulation rate, in adolescents with McCune-Albright syndrome (MAS) and a history of peripheral precocious puberty. Design: Prospective cross-sectional study. Setting: Academic center. Patient(s): A total of eight adolescents with MAS were compared with 15 healthy adolescents matched by age, Tanner stage and body mass index. Intervention(s): We determined basal gonadotropins, sex steroids, sex hormone binding globulin, anti-Müllerian hormone, glucose and insulin. A leuprolide acetate test was performed to measure luteinizing hormone (LH) and follicle stimulating hormone (FSH) (at 0 and 3 h), and 17B-estradiol, testosterone and 17-OH-progesterone (at 0 and 24 h). Salivary progesterone levels were used to assess ovulation during the 13th, 18th, 23rd and 28th days of each menstrual cycle for three to five consecutive cycles, and one pelvic ultrasound was performed during the follicular phase. Main outcome measure(s): Ovulation rate in adolescents with MAS. Result(s): The proportion of ovulatory cycles was 52.6% in controls compared with 35.7% in patients with MAS. Conclusion(s): The adolescent girls with MAS appear to have a lower ovulatory rate compared with controls.

Deterioro cognitivo leve y enfermedad de Alzheimer inicial en adultos mayores

The early detection of dementia carries implications for clinical management of patients and their families, and it is of utmost concern if an effective pharmacological treatment is to be found. We report the final clinical diagnosis of 36 seniors who complained (or were accused) of forgetfulness. In the Initial Mini-Mental State Examination they scored 25 to 30 out of 30 points and could be diagnosed as having Mild Cognitive Impairment without dementia; preclinical Alzheimers disease was suspected. Clinical observation (from 6 to 70 months, mean 31) showed that the clinical condition of 15 patients clearly worsened; these were diagnosed as likely Alzheimers disease patients. Eleven suffered from emotional disturbances and improved with pharmacological and psychosocial treatment; ten of the patients had a static condition and remained in the Mild Cognitive Impairment category. We discuss the frontiers between normal aging, Mild Cognitive Impairment and Alzheimers disease; we remark the difficulties in the differential diagnosis. Most of the patients with Alzheimers disease were anosognosics with regard to the memory impairment; this could be a useful clinical point. We also underscore the usefulness of a neuropsychological assessment and the need for continued longitudinal evaluation of subjects with questionable dementia. In the next years, progress in neuropsychological, radiological and biological examinations will lead to improve diagnoses

New Diagnostic Criteria of Polycystic Ovarian Morphology for Adolescents: Impact on Prevalence and Hormonal Profile

Background: The ultrasonographic criteria used to identify polycystic ovarian morphology (PCOM) during adolescence have changed over time. Recently, a Worldwide Pediatric Consensus (PedC) defined PCOM using stricter criteria than the previous recommendations of the Rotterdam Consensus (RC) and Androgen Excess-Polycystic Ovarian Syndrome Society (AES/PCOS) criteria. The aim of this study was to determine the prevalence of PCOM in healthy adolescents according to the 3 reported diagnostic criteria and compare the hormonal profile in females with and without PCOM based on the PedC criteria. Methods: Nonobese adolescents (n = 102) with regular menstrual cycles were studied. Transabdominal ultrasound and hormonal profiles were assessed during the follicular phase. PCOM was defined on the basis of the 3 published criteria. Results: On the basis of the PedC, RC, and AES/PCOS criteria, PCOM was diagnosed in 13, 34, and 24% of adolescents, respectively. Adolescents with and without PCOM according to the PedC criteria had similar androgen levels. Serum anti-Müllerian hormone (AMH) levels were elevated in adolescents with PCOM, irrespective of the criteria used. Conclusions: Use of the new PedC diagnostic criteria for PCOM results in a lower prevalence of this ultrasonographic pattern in adolescents, but this condition is not associated with hyperandrogenism. Elevated AMH is associated with PCOM in adolescents regardless of the criteria used to determine the ultrasonographic pattern.

Pregestational type 2 diabetes and gestational diabetes exhibit different sexual steroid profiles during pregnancy

Abstract Higher androgen levels are observed in non-pregnant women with diabetes. Whether this hormonal profile is found during pregnancy is unknown. The aim of this study was to determine the sexual steroids levels in pregnant women with pregestational type 2 (T2D) and gestational diabetes (GD) compared to healthy control (C) pregnant women during the second half of pregnancy. A prospective study of 69 pregnant women with T2D (n = 21), GD (n = 24) and control (C, n = 24) was followed up during the second half of gestation. Clinical assessments and blood samples were collected at 26.7 (25–27.8); 34 (32–34.9) and 37.5 (37–40) weeks of gestation. Androgens, sex hormone-binding globulin (SHBG), estrogens, estradiol/testosterone (E/T) ratio, insulin, glucose, HOMA-IR, were measured. Testosterone, insulin and homeostatic model assessment of insulin resistance (HOMA-IR) levels were higher in T2D compared with C at each sampling point during pregnancy, even after adjusting for BMI and age. Estrogens levels and estradiol/testosterone ratio were lower in T2D and GD compared with C. Hyperandrogenemia, and higher insulin resistance is observed in T2D, but not in GD during pregnancy. Decreased estrogen and E/T ratio found in T2D and GD suggests a diminished aromatase activity during gestation. T2D and GD are associated with specific changes in sexual steroids and insulin resistance levels during pregnancy.

The use of long-acting reversible contraceptives in Latin America and the Caribbean: current landscape and recommendations

Abstract STUDY QUESTION Can the high rate and associated burden of unintended pregnancy (UP) and adolescent pregnancy in Latin America and the Caribbean (LAC) be reduced through wider access to and use of long-acting reversible contraceptive (LARC) methods? SUMMARY ANSWER Studies show that impoved access to and use of LARC methods is an effective tool for reducing the high rates of UP, unsafe abortion and abortion-related complications, and maternal deaths (as well as reducing their social and financial burden), and we have provided recommendations to help achieve this in LAC. WHAT IS KNOWN ALREADY LAC comprises 46 countries with 650 million inhabitants, and shows large disparities in socioeconomic development, access to health services and attention to sexual and reproductive health rights. The exercise of these rights and universal access to sexual and reproductive health (SRH) programmes is a key strategy for improving maternal health by reducing the number of UPs, the rate of women’s and child mortality and morbidity, and the number of unsafe abortions. The implementation of SRH programmes in the region has contributed to a decrease in pregnancy rates of more than 50% over 40 years. However, despite this progress, the numbers of UP and adolescent pregnancies are still among the highest worldwide, which can be attributed in large part to the low prevalence of use of LARC methods. STUDY DESIGN, SIZE, DURATION This is a position paper with the objective of reviewing the magnitude and burden of UP in LAC, as well as available LARC methods and barriers to their access, with the goal of increasing knowledge and awareness among healthcare professionals (HCP), policymakers and the general public about the potential to reduce UP rates through the increased use of LARC. PARTICIPANTS/MATERIALS, SETTING, METHOD We searched the electronic databases of PubMed and EMBASE to identify studies published up to May 2017. We also searched for websites regarding LAC, LARC methods, and UP including, for example, those from the United Nations, the World Health Organization, Pan American Health Organization, the Alan Guttmacher Institute and the United States Agency for International Development. Studies were included if they investigated mainly UP and their consequences as well as the use of LARC methods in the region. During 3 days of meetings, the importance of the studies identified and the appropriateness of inclusion were discussed. MAIN RESULTS AND THE ROLE OF CHANCE LAC is not one unit and shows great ethnic diversity as well as economic and cultural differences among the various countries. These differences must be taken into account when developing policies related to disseminating information and combatting misinformation regarding the use of LARC among different audiences, such as adolescents and young women, nulligravidas, indigenous populations and women with disabilities. Furthermore, only some governments have made efforts to increase accessibility to LARC methods, and there is a need to implement training programmes for HCPs, launch education campaigns for the general public, increase access and review the cost-benefit analyses specific to LARC, which have already demonstrated that the upfront cost of LARC is less than the cummulative expense of short-term contraceptives. Recommendations to achieve these goals are presented. LIMITATIONS, REASONS FOR CAUTION Knowledge and awareness of the contraceptive method itself and of the mix of individual countries in the region is essential to the development of specific strategies and actions, tailored to each particular country situation, aimed at increasing access to modern contraceptive methods, especially LARC. WIDER IMPLICATIONS OF THE FINDINGS Healthcare systems in LAC should consider LARC as a primary option for decreasing UP and adolescent pregnancy. Disseminating information, increasing awareness of their efficacy, removing barriers and improving access to LARC methods are the urgent actions recommended for government, academia, professional organizations, insurance companies and policymakers in order to address this major public health problem in LAC. STUDY FUNDING/COMPETING INTERESTS This manuscript was supported by a grant from the Americas Health Foundation (AHF), a 501(c)3 nonprofit organization dedicated to improving healthcare throughout the Latin American Region. LB and IM received additional support from the São Paulo Research Foundation (FAPESP) award # 2015/20504-9. The authors declare no conflict of interest.

Hyperandrogenism in adolescent girls: relationship with the somatotrophic axis.

Abstract Background: During puberty there is a physiologic increase in adrenal and ovarian androgens. It has been suggested that the somatotrophic axis may be related to the development of hyperandrogenism and anovulation in non-obese adult women with polycystic ovarian syndrome (PCOS). The objective of the study was to investigate whether ovarian androgen secretion in young postmenarchal girls is related to the function of their somatotropic axis. Methods: This was a cross-sectional study of adolescent girls. We studied non-obese adolescent girls with hyperandrogenism (HA; n = 21) matched with control girls (C; n = 25) for chronological age, age at menarche and body mass index. We obtained a fasting blood sample for measurement of serum glucose, insulin, 17-hydroxyprogesterone (17OH-Prog), dehydroepiandrosterone-sulfate (DHEA-S), androstenedione, sex hormone-binding globulin (SHBG), total testosterone, IGF-I, IGF-II, IGFBP-1, IGFBP-3, ghrelin, leptin, AMH (antiMüllerian hormone), luteinizing hormone (LH) and follicle stimulating hormone (FSH) during the follicular phase of the menstrual period. We performed an oral glucose tolerance test to determine blood glucose, insulin and ghrelin levels and urine samples to measure urinary GH (growth hormone) levels. Results: As expected, the hyperandrogenic girls had significantly higher Ferriman scores, basal total testosterone, free androgen index (FAI), androstenedione, AMH, and basal LH levels compared with the girls in controls. Serum IGF-I, IGF-II, IGFBP-3 and urinary GH did not differ between HA and C. There was a correlation between urinary GH and FAI in all girls (r 0.29, p < 0.05). In addition, in HA girls FAI correlated with insulin, homeostasis model assessment (HOMA) and ghrelin. Conclusions: We observed a correlation between urinary GH and FAI in the hyperandrogenic and control girls, suggesting that the function of the somatotrophic axis may influence the secretion of androgens in adolescent girls.