Pharmaceutical and Pharmacological Evaluation of the Effect of Nano-Formulated Spironolactone and Progesterone on Inflammation and Hormonal Levels for Managing Hirsutism Experimentally Induced in Rats.

Hirsutism is a dermatological condition that refers to the excessive growth of hair in androgen-sensitive areas in women. Recently, the enhancement of the visible signs of a hairy female has taken special concern that affected the quality of life. The present study was developed to compare the follicular targeting effect of topical spironolactone (SP) or progesterone (PG)-loaded nanostructured lipid carrier (NLC) on the management of hirsutism. Four NLC formulations were prepared using cold homogenization techniques and pharmaceutically evaluated. SP-NLC and PG-NLC topical hydrogels were prepared to explore their pharmacological effect on letrozole induced polycystic ovarian syndrome (PCOS) in rats. Inflammatory mediators, antioxidant, and hormonal parameters were assayed. Additionally, histopathological examination was carried out to confirm the successful induction of PCOS. Results confirmed that all NLC formulations have a spherical shape with particle size ranged from 225.92 ± 0.41 to 447.80 ± 0.66 nm, entrapment efficiency > 75%, and zeta potential (- 31.4 to - 36.5 mV). F1 and F3 NLCs were considered as selected formulations for SP and PG, respectively. Female Wistar rats treated with F1 formulation for 3 weeks displayed better outcomes as manifested by the measured parameters as compared to the other tested groups. A significant reduction in hair follicle diameter and density was observed after topical application of SP or PG nano-gels. Finally, the outcomes pose a strong argument that the development of topically administered SP-NLC can be explored as a promising carrier over PG-NLC for more effectual improvement in the visible sign of hirsutism.

New-onset hirsutism.

This postmenopausal patient developed hirsutism following a surgical procedure. Thorough lab work directed us to the unusual cause.

Clinical and biochemical signs of polycystic ovary syndrome in young women born preterm.

OBJECTIVE: It has been suggested that adverse early life exposures increase the risk of developing polycystic ovary syndrome (PCOS) in later life. We hypothesized that women born preterm would have more biochemical and clinical signs of PCOS than women born at term. DESIGN: The ESTER Preterm Birth Study participants were born in Northern Finland and identified from the Northern Finland Birth Cohort and the Finnish Medical Birth Register. Altogether, 74 women born very or moderately preterm (<34 gestational weeks, VMPT), 127 born late preterm (at 34-36 weeks, LPT), and 184 born full term (≥37 weeks, controls) were included in the analysis (mean age: 23.2 years). METHODS: We measured serum total testosterone and sex hormone-binding globulin (SHBG) and calculated the free androgen index (FAI). PCOS according to the clinical and biochemical signs was defined either as hirsutism and oligoamenorrhea (via questionnaire) or as oligoamenorrhea and elevated testosterone levels (>2.4 nmol/L). RESULTS: Women born VMPT/LPT exhibited 33.0% (8.7, 62.8)/16.4% (-2.0, 38.1) higher testosterone, 28.5% (5.3, 45.9)/24.1% (5.6, 38.9) lower SHBG levels, and 64.6% (19.4, 127.1)/42.5% (11.1, 82.9) higher FAI than controls after adjusting for age and recruitment cohort, maternal BMI, smoking, and pregnancy disorders, parental education, history of hypertension, diabetes, myocardial infarction or stroke, and subject's birth weight s.d. Odds ratios for having PCOS were 1.67 (0.44, 6.23)/3.11 (1.26, 7.70). CONCLUSIONS: Women born preterm have a more hyperandrogenic hormonal profile, and those born LPT are approximately three times more likely at risk to have PCOS compared to women born at term.

SHBG as a Marker of NAFLD and Metabolic Impairments in Women Referred for Oligomenorrhea and/or Hirsutism and in Women With Sexual Dysfunction.

PCOS is one of the most common endocrine disorders and NAFLD is one of its most dangerous metabolic consequences. The diagnosis of NAFLD is not a practical task and the condition is at risk of being overlooked. The use of simpler but still reliable surrogate markers is necessary to identify women with a high likelihood of NAFLD. The aim of this study was to evaluate the clinical correlates of NAFLD Liver Fat Score (NAFLD-LFS) in women with oligomenorrhea and/or hirsutism. Furthermore, the study aimed to evaluate whether, among the hormonal parameters evaluated in such women, possible hallmarks of NAFLD may be identified. To this purpose, 66 women who attended our Outpatient Clinic for oligomenorrhea and/or hyperandrogenism were included in the study. In order to validate the results obtained in the first cohort, a second independent sample of 233 women evaluated for female sexual dysfunction (FSD) was analyzed. In cohort 1, NAFLD-LFS positively correlated with metabolic and inflammatory parameters. Among the hormone parameters, NAFLD-LFS showed no significant relationships with androgens but a significant negative correlation with SHBG (p<0.0001) that therefore appeared as a candidate hallmark for pathologic NAFLD-LFS. The ROC analysis showed a significant accuracy (81.1%, C.I.69.1-93.0, p <0.0001) for SHBG in identifying women with a pathological NAFLD-LFS. In particular, a SHBG 33.4 nmol/l was recognized as the best threshold, with a sensitivity of 73.3% and a specificity of 70.7%. In order to validate this SHBG as a marker of metabolic impairment possible related with the presence of NAFLD, we tested this threshold in cohort 2. FSD women with SHBG <33.4 nmol/l had worse metabolic parameters than women with SHBG ≥33.4 nmol/l and a significantly higher NAFLD-LFS even after adjusting for confounders (B=4.18 [2.05; 6.31], p=0.001). In conclusion, this study provides a new evidence in the diagnostic process of NAFLD, showing that the measurement of SHBG, which is routinely assessed in the workup of women referred for possible PCOS, could identify women at higher metabolic risk, thus detecting those who may deserve further targeted diagnostic assessment.

Androgens and hirsutism score of overweight women with polycystic ovary syndrome improved after vitamin D treatment: A randomized placebo controlled clinical trial.

BACKGROUND & AIM: The objective of this study was to investigate the effect of vitamin D treatment on androgen levels and hirsutism scores in overweight women with PCOS. METHODS: A prospective, randomized, double-blind, placebo-controlled clinical study was conducted at King Abdullah University Hospital in Irbid, Jordan. Overweight Jordanian females aged 18-49 years with vitamin D deficiency and PCOS (n = 60) were assigned to two groups: the treatment group (n = 30) who received 50,000 IU per week of vitamin D3 and the control group (n = 30) who received a placebo. RESULTS: After receiving the treatment for 12 consecutive weeks, the levels of total testosterone, parathyroid hormone, free androgen index, and hirsutism score were significantly decreased (P < 0.001), and the levels of 25-hydroxyvitamin D (25(OH)D), sex hormone binding globulin, and phosphorus were significantly increased (P < 0.05). Furthermore, significant changes were observed in ovarian volume and follicle numbers and size ultrasonography, and in the regularity of the menstrual cycle (P < 0.001). In the placebo group, no significant changes were observed in either androgen levels, hirsutism score, or menstrual regularity. CONCLUSION: Vitamin D3 at a treatment dose of 50,000 IU per week improved 25(OH)D levels and decreased the hirsutism scores and androgen levels of overweight women with PCOS. These results could mean increased fertility and better reproductive health for overweight women with PCOS; the use of vitamin D3 as a treatment for these patients should be further investigated. CLINICALTRIALS. GOV REGESTRATION NUMBER: NCT02328404.

Reproductive Hormones and Anthropometry: A Follow-Up of PCOS and Controls From Perimenopause to Older Than 80 Years.

CONTEXT: There is a lack of knowledge about hormonal and anthropometric changes in women with polycystic ovary syndrome (PCOS) after the menopause. OBJECTIVE: This work aimed to study reproductive hormones and anthropometry in women with PCOS older than 80 years. DESIGN AND SETTING: This prospective cohort study was conducted at a university hospital. PATIENTS: A well-defined cohort of women with PCOS, previously examined in 1987 and 2008 (21 years) was reexamined in 2019 (11 years). Of the original cohort (n = 37), 22 women were still alive and 21 (age range, 72-91 years) participated. Comparisons were made with age-matched controls (n = 55) from the original control cohort (body mass index [BMI] similar to PCOS women). The results were compared with results from 1987 and 2008. INTERVENTIONS: Hormonal measurements and a physical examination were performed. MAIN OUTCOME MEASURES: Follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), hirsutism score, BMI, and waist to hip ratio (WHR) were measured. RESULTS: At mean age 81 years, FSH levels were lower in women with PCOS (50 vs 70 IU/L) who were still more hirsute than controls (33% vs 4%). No differences were found in FAI, testosterone, SHBG or LH levels, BMI, or WHR. From perimenopausal age until the present age, levels of testosterone and FAI continued to decline in women with PCOS. SHBG levels continued to increase with age. FSH had not changed over time during the last 11 years. CONCLUSIONS: Women with PCOS at age 72 to 91 had lower FSH levels, remained clinically hyperandrogenic, and had similar FAI and body composition as controls.

The role and importance of auxiliary tests in differential diagnosis in patients with mildly high basal 17-OH-progesterone levels in the evaluation of hirsutism

Background/aim: In the differential diagnosis of hirsutism, early follicular basal 17-OH-progesterone levels sometimes overlap with the diagnosis of late onset congenital adrenal hyperplasia (LOCAH) and other causes of hyperandrogenism. This study aims to investigate the role of some common tests and clinical findings in differential diagnosis in such cases. Materials and methods: One hundred seventy-five female patients with hirsutism and mildly high initial 17-OH-progesterone levels (2-10 ng/mL) were included in the study. The cases were divided into three groups according to their diagnosis: LOCAH (n = 16, mean age = 26.1 ± 6.9), polycystic ovary syndrome (PCOS) (n = 122, mean age = 23.9 ± 5.1), and intracranial hypertension (IH) (n = 37, mean age = 25.2 ± 7.3). Clinical signs and symptoms, such as menstrual irregularity and hirsutism score, and hormone levels including total testosterone and dehydroepiandrosterone sulfate (DHEAS), were compared between the groups. Results: There was no difference between the groups with PCOS, LOCAH, and IH for total testosterone level results (P = 0.461). The DHEAS level was higher in the PCOS group than in the LOCAH group (449.6 ± 151.14 vs. 360.31 ± 152.40, P = 0.044). While there was no difference between the PCOS and LOCAH groups in terms of menstrual irregularity (P = 0.316), the hirsutism score for IH was significantly lower than those of PCOS and LOCAH (9.2 vs. 12.2 and 11.1, respectively; P < 0.001). Basal 17-OH-progesterone levels were higher in the LOCAH group than in the other groups (P = 0.016). Conclusion: While DHEAS level was lower in LOCAH than in PCOS, it was not different from that in IH. While the severity of hirsutism was higher in LOCAH than in IH, it was not different from that in PCOS. Menstrual irregularity was similar between PCOS and LOCAH. According to these results, although the auxiliary tests and clinical findings for the diagnosis of LOCAH contribute to the clinical interpretation, they are not superior to the 17-OH-progesterone level for diagnosis.

Screening for Androgen Excess in Women: Accuracy of Self-Reported Excess Body Hair Growth and Menstrual Dysfunction.

CONTEXT: Epidemiologic studies of polycystic ovary syndrome (PCOS) are limited, especially in populations where diagnostic resources are less available. In these settings, an accurate, low-cost screening tool would be invaluable. OBJECTIVE: To test the use of a simple questionnaire to identify women at increased risk for PCOS and androgen excess (AE) disorders. STUDY DESIGN: Prospective cohort study from 2006-2010. SETTING: Community-based. PARTICIPANTS: Women aged 14 to 45 years. INTERVENTION: A screening telephone questionnaire consisting of 3 questions was tested, where participants were asked to self-assess the presence/absence of male-like hair and menstrual irregularity. Participants were then invited to undergo a direct examination, including completing a medical history and undergoing a modified Ferriman-Gallwey (mFG) hirsutism score, ovarian ultrasound, and measurement of circulating total and free testosterone, DHEAS, TSH, prolactin and 17-hydroxyprogesterone levels. MAIN OUTCOME MEASURE: Accuracy of questionnaire in predicting PCOS, AE, and irregular menses. RESULTS: Participants with self-assessed irregular menses and/or excess hair were labeled "Possible Androgen Excess (Poss-AE)" and those self-assessed with regular menses and no excess hair were labeled "Probable Non-Androgen Excess (Non-AE)." The study was completed in 206/298 (69%) of the Poss-AE and in 139/192 (73%) of the Non-AE. Of Poss-AE and Non-AE subjects, 82.5% and 15.8%, respextively, presented with PCOS. The calculated sensitivity, specificity, positive predictive value, and negative predictive value of the 3-question telephone survey to predict PCOS was 89%, 78%, 85%, and 83%, respectively. CONCLUSIONS: A simple telephone questionnaire, based on self-assessment of body hair and menstrual status, can be used with a high predictive value to identify women at risk for AE disorders, including PCOS, and to detect healthy controls. This approach could be an important tool for needed epidemiologic studies.

The role of androgen receptor CAG repeat polymorphism in androgen excess disorder and idiopathic hirsutism.

PURPOSE: The study aimed to investigate whether repeat number in the androgen receptor (AR) gene has any contribution to phenotypes of the disease of androgen excess (polycystic ovary syndrome (PCOS), idiopathic hyperandrogenemia (IHA) and idiopathic hirsutism (IH) in a cohort of Turkish women. METHODS: Three hundred and fifty-four voluntary premenopausal women (172 healthy controls and 182 patients with androgen excess disorders and idiopathic hirsutism) 18-45 years of age seen at an outpatient endocrine clinic at Erciyes University Hospital between January 2013 and December 2014 were included. All volunteers have undergone physical examination and biochemical evaluation. The polymorphic (CAG)n repeat of the human AR was determined by fragment analyses. RESULTS: Detailed clinical analyses of the patients ended up with 137 PCOS, 24 IHA, and 21 IH. Pairwise comparisons revealed the CAG repeat number differences between the PCOS and controls (p = 0.005) and IH and controls (p = 0.020). Women with CAG repeat length ≤ 17 had a significantly increased twofold risk for PCOS than those women with > 17 CAG repeats OR: 2.0 (95% CI 1.2-3.3, p = 0.005). Women with CAG repeat length ≤ 17 had a significantly increased threefold risk for IH than those women with > 17 CAG repeats OR: 2.9 (95% CI 1.2-7.3, p = 0.020). When correlation analysis was performed, a weak negative correlation was detected between the short allele and FGS score (r = - 0.131, p = 0.013) and a positive relationship between total testosterone and longer allele in the IHA group (r = 0.425, p = 0.039). Median repeat length of the shorter allele between oligomenorrhea and woman with normal menstrual cycle was found to be statistically significant (p = 0.017). CONCLUSION: This study indicated that the risk of PCOS and IH is associated with the inheritance of ARs with shorter CAG repeats.

Distribution of Body Hair in Young Australian Women and Associations With Serum Androgen Concentrations.

CONTEXT: An important element of the diagnosis of polycystic ovary syndrome is hyperandrogenism. OBJECTIVE: To determine the distribution of modified Ferriman-Gallwey (mF-G) scores, as a measure of facial and body hair growth, and associations between the mF-G scores and serum androgen concentrations, including 11-oxygenated androgens. DESIGN: Cross-sectional study of non-health-care-seeking women, aged 18 to 39 years, recruited from the eastern states of Australia from November 2016 to July 2017. PARTICIPANTS AND MEASUREMENTS: Participants provided an mF-G self-assessment that corresponded to their appearance when not using treatment for excess hair. Androgens were measured in 710 women by liquid chromatography and tandem mass spectrometry. RESULTS: The distribution of the mF-G scores was right-skewed. The median (range) mF-G score of all participants (73.1% Caucasian) was 5 (0-36). The mF-G scores were negatively associated with age (rs = 0.124; P < 0.0001) and positively associated with body mass index (BMI) (rs = 0.073; P < 0.0001). Only androstenedione remained significantly associated with mF-G scores when controlling for age and BMI. Cluster analysis identified 2 groups with mF-G score of < 10 and ≥ 10. Repeating the cluster analysis using the combined vector of mF-G score and androstenedione returned a similar cluster structure, and again separated the 2 groups at a mF-G score < 10 versus ≥ 10. CONCLUSIONS: A self-assessed mF-G score ≥ 10 is indicative of excess body hair. Androstenedione, as well as testosterone, should be measured when hyperandrogenism is being evaluated. The lack of association between mF-G scores and the 11-oxygenated androgens highlights the need for a better understanding of these steroids.

A novel biochemical marker -OKL38- with its apoptotic and antioxidant properties for the development of PCOS and its related clinical implications.

Aim: To investigate the role of serum OKL38 levels in the development of polycystic ovary syndrome (PCOS) and clinical implications related to PCOS.Method: PCOS (n = 33) and ovulatory controls (n = 48) were recruited for the study. Anthropometric measurements were recorded, and blood samples for hormonal and biochemical parameters including serum OKL38 levels were obtained. The potential role of OKL38 on the development of PCOS, metabolic syndrome and cardiovascular disease (CVD) were investigated. Framingham risk score (FRS) was used for the determination of CVD risk.Results: Mean Ferriman-Gallway (FG) score, insulin, low-density lipoprotein (LDL), total cholesterol (TC) levels, and the homeostasis model assessment of insulin resistance index (HOMA-IR) were significantly increased (p < .05) in women with PCOS compared to controls. PCOS group had lower mean OKL38 level compared to controls (p < .0001) and OKL38 was negatively predictive for the diagnosis of PCOS after adjustment of variables that were significantly different between two groups. A negative association between OKL38 and metabolic syndrome in PCOS women was evident after adjustment for age, obesity, and abdominal obesity. OKL38 level was also negatively correlated with body mass index, waist-to-hip-ratio, fat composition, serum TC, LDL, free testosterone levels, FRS, and FG scores.Conclusion: OKL38 may have a partial role in the etiopathogenesis of PCOS and may protect development of metabolic syndrome and CVD in women with PCOS.

Long-term treatment with α-lipoic acid and myo-inositol positively affects clinical and metabolic features of polycystic ovary syndrome.

The aim of this retrospective study was to evaluate the effects of a long-term treatment with α-lipoic acid (ALA) combined with myo-inositol (MI) on clinical and metabolic features of women with polycystic ovary syndrome (PCOS). Fifty-seven women with PCOS and a history of oligoamenorrhea were treated with MI and ALA (800 mg + 2000 mg per day). Forty-four of them had complete clinical charts and were considered eligible for the study. Information about cycle length and body mass index (BMI) was checked after 6, 12, and 24 months. After 12 months ovarian volume, total testosterone plasma levels and changes in hirsutism were also evaluated. The metabolic parameters were evaluated in 16 women after 6 and 18 months of the treatment. Cycle length was significantly reduced at 6 (p < .001), 12, and 24 months of treatment (p < .01). BMI showed a reduction only at 6 months (p < .05), thereafter returning similar to the basal values. No changes of testosterone and ovarian volume were observed. HOMA-IR and fasting insulin were unchanged, but the insulin response to a 3 h OGTT was improved after 6 (p < .01) and 18 months (p < .05) of treatment. No individual suffered from any adverse event. In conclusion, the combination of ALA and MI showed to be useful as long-term therapy in PCOS women, providing a normalization of the menstrual cycle and an amelioration of insulin levels with a high tolerability.

Evaluation of serum level of omentin-1 in females with hirsutism.

BACKGROUND: Hirsutism is a common clinical condition encountered in day-to-day practice. The androgenic causes account for more than 80% of these patients and include polycystic ovary syndrome (PCOS), which affects about 70%-80% of hirsute women. The second most common cause is idiopathic hirsutism. Omentin-1 is an adipokine mainly produced by visceral adipose tissue. AIM: The current study aimed at evaluating omentin-1 levels in hirsute females with PCOS and in idiopathic hirsutism. PATIENTS AND METHODS: Eighty-five females were included in this study. They were classified into three groups: thirty hirsute patients with PCOS, thirty females with idiopathic hirsutism, and twenty-five healthy control females. The participants were subjected to history taking, physical and dermatological examination. A gynecological history and radiological examination of the ovary also were done. Serum testosterone and omentin-1 were measured by ELISA. RESULTS: Serum testosterone was statistically elevated in PCOS than other groups. Serum omentin-1 in females with idiopathic hirsutism was statistically significantly higher than control and PCOS. There was a significant inverse correlation between serum testosterone level and serum omentin-1 level. CONCLUSION: Omentin-1 may be involved in the pathogenic process of hirsutism.

First Report of Retroperitoneal Mucinous Cystadenoma in a Patient with Hirsutism.

Primary retroperitoneal mucinous cystadenomas (PRMC) are rare benign neoplasms with only 55 documented cases in the English literature so far. A 19-year-old female exhibited hirsutism and was found to have a cystic mass measuring 5.8 cm × 3.9 cm × 5.8 cm in the left retroperitoneum. During subsequent work up, a high pre-operative value of dehydroepiandrosterone sulfate (DHEA-S) was noted. The patient was referred to surgical oncology and underwent an uneventful laparoscopic cystectomy. Pathology classified the cyst as PRMC. Post-operatively, the patient's DHEA-S levels normalized, though there was no appreciable decrease in the patient's hirsutism in the short-term follow-up. The origin of PRMC is uncertain. Due to their unknown biological potential, surgical resection is usually recommended. To the best of our knowledge, this is the first report documenting a PRMC and elevated levels of androgens in conjunction with hirsutism.

Clinical and hormonal characteristics in heterozygote carriers of congenital adrenal hyperplasia.

Non-classical congenital adrenal hyperplasia (NC-CAH) includes a group of genetic disorders due to a broad class of CYP21A2 variants identifying a disease-causing 'C' genotype. The heterozygous carriers of CYP21 mutations are at increased risk of developing clinically evident hyperandrogenism, even though clinical and laboratory characteristics are still underestimated. With the aim of obtaining a more accurate delineation of the phenotype of heterozygous carrier of CAH, we analyzed clinical, biochemical and molecular characteristics in a cohort of Sicilian subjects. Fifty-seven females with biallelic and monoallelic CYP21A2 variants classifying NC-CAH (24) and heterozygous carriers of CAH (33), respectively were selected. Forty-four females age-matched healthy controls were also enrolled and genotyped for CYP21A2. Clinical, hormonal and genetic data were collected. CYP21A2 monoallelic mutations, defining the heterozygous carriers state, were identified in subjects with clinical features including hirsutism, oligomenorrhoea, overweight and a PCO-like phenotype, particularly occurring in the age of adolescence. Consistently, levels of 17OHP and cortisol were found to be significantly different from NC-CAH. Overall, some clinical and laboratory findings including oligomenorrhea and 17OHP/cortisol ratio were observed as independent markers associated with carriers of CAH. Here we report a high prevalence of late-onset signs of polycystic ovary syndrome (PCOS) and hyperandrogenism in heterozygous carriers. The 17OHP/cortisol ratio may be a predictive tool to identify the carriers of CAH, even though specific cut-off values have not yet been identified.

The Modified Ferriman-Gallwey Score and Hirsutism among Filipino Women.

BACKGROUND: The modified Ferriman-Gallwey (mFG) score is the gold standard for the clinical evaluation of hirsutism. However, racial variations in terminal hair growth limit this tool. This study aimed to determine the mFG cut-off score among Filipino women and its association with biochemical hyperandrogenism. METHODS: A total of 128 Filipino women were included in this prospective cross-sectional study and were divided into two groups: a polycystic ovary syndrome (PCOS) group (n=28) and a non-PCOS group (n=100). The participants underwent mFG score determination, ovarian ultrasound conducted by a single sonographer, and hormone testing. The mFG cut-off score was determined based on the 95th percentile of the non-PCOS group. Logistic regression was used to analyze the relationship between mFG score and biochemical hyperandrogenism. RESULTS: Although the mFG score was generally low in both the PCOS and non-PCOS groups, the former exhibited a higher mean score than the latter (4.3±3.0 vs. 2.0±2.2, P<0.001). Normal values for the total mFG score ranged from 0 to 7. Using a cut-off score of 7, a higher proportion of hirsute women (mFG score ≥7) was observed in the PCOS group versus the non-PCOS group (17.9% vs. 5.0%, P=0.025). Elevated calculated free testosterone (FT) was also found to be significantly associated with hirsutism (odds ratio, 6.2; 95% confidence interval, 1.2 to 32.4 pmol/L; P=0.030). CONCLUSION: A score of 7 and above constitutes hirsutism in this population of Filipino women. Hirsute women are more likely than non-hirsute women to have elevated calculated FT.

Serum Prostate-Specific Antigen Level in Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis.

We undertook a comprehensive search of all published original articles evaluating the diagnostic value of prostate-specific antigen (PSA) for the detection of polycystic ovary syndrome (PCOS). Finally, 25 studies with a total of 1865 participants (1104 cases and 761 controls) met the inclusion criteria. Mean serum PSA levels were significantly higher in PCOS women compared to healthy women [Standardized mean difference (SMD)=1.73 ng/ml, 95% CI=1.22 to 2.25, p<0.001]. Only 5 studies reported accuracy indicators and were included in the bivariate random-effects model; with a total of 509 samples that included 332 (65.22%) confirmed PCOS women. The sensitivity of serum PSA for the diagnosis of PCOS varied between 66.3 and 90.6%, and, the specificity ranged from 62.5-86.7%. Meta-analysis revealed a pooled sensitivity of 72.3% (95% CI 67.1-77.00%) and specificity of 74.6% (95% CI 67.5-80.8%) with an area under the summary ROC curve equal to 0.82 (95% CI 0.75-0.83). The summary estimates were 2.92 (95% CI 1.98-4.31) for positive LR and 0.37 (95% CI 0.26-0.51) for negative LR. The pooled estimate of diagnostic odds ratio (DOR) of serum PSA was 9.01 (95% CI 4.35-18.64). Considering the methodological weaknesses existed in studies, lack of sufficient data regarding the accuracy indicators, and the complexity of the exact pathophysiology of PSA secretion in women, the precise position of PSA, as a diagnostic test for the detection of PCOS, in clinical practice is undetermined, and further studies are still needed.

Vitamin D and probiotic co-supplementation affects mental health, hormonal, inflammatory and oxidative stress parameters in women with polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to determine the effect of vitamin D and probiotic co-administration on mental health, hormonal, inflammatory and oxidative stress parameters in women with polycystic ovary syndrome (PCOS). METHODS: This randomized, double-blinded, placebo-controlled clinical trial was carried out on 60 subjects, aged 18-40 years old. Subjects were randomly allocated to take either 50,000 IU vitamin D every 2 weeks plus 8 × 109 CFU/day probiotic (n = 30) or placebo (n = 30) for 12 weeks. RESULTS: Vitamin D and probiotic co-supplementation, compared with the placebo, significantly improved beck depression inventory [ß (difference in the mean of outcomes measures between treatment groups) - 0.58; 95% CI, - 1.15, - 0.02; P = 0.04], general health questionnaire scores (ß - 0.93; 95% CI, - 1.78, - 0.08; P = 0.03) and depression, anxiety and stress scale scores (ß - 0.90; 95% CI, - 1.67, - 0.13; P = 0.02). Vitamin D and probiotic co-supplementation was associated with a significant reduction in total testosterone (ß - 0.19 ng/mL; 95% CI, - 0.28, - 0.10; P < 0.001), hirsutism (ß - 0.95; 95% CI, - 1.39, - 0.51; P < 0.001), high-sensitivity C-reactive protein (hs-CRP) (ß - 0.67 mg/L; 95% CI, - 0.97, - 0.38; P < 0.001) and malondialdehyde (MDA) levels (ß - 0.25 µmol/L; 95% CI, - 0.40, - 0.10; P = 0.001), and a significant increase in total antioxidant capacity (TAC) (ß 82.81 mmol/L; 95% CI, 42.86, 122.75; P < 0.001) and total glutathione (GSH) levels (ß 40.42 µmol/L; 95% CI, 4.69, 76.19; P = 0.02), compared with the placebo. CONCLUSIONS: Overall, the co-administration of vitamin D and probiotic for 12 weeks to women with PCOS had beneficial effects on mental health parameters, serum total testosterone, hirsutism, hs-CRP, plasma TAC, GSH and MDA levels. TRIAL REGISTRATION: This study was retrospectively registered in the Iranian website ( www.irct.ir ) for registration of clinical trials ( IRCT20170513033941N37 ).

Minimal difference in phenotype between adolescents and young adults with polycystic ovary syndrome.

OBJECTIVE: To test the hypothesis that the polycystic ovary syndrome (PCOS) phenotype, or its component features, is less severe in adolescents than in young adult patients, in a referred (clinical) population. DESIGN: Cross-sectional study. SETTING: Tertiary-care academic medical center. PATIENT(S): Two hundred seventy-four adolescents and young adults aged 13.0-24.9 years with PCOS according to the National Institute of Health 1990 criteria. Patients were categorized as adolescents (AD: 13.0-18.9 years; n = 91) and young adults (YA: 19.0-24.9 years; n = 183). Adolescents were further categorized as early adolescents (Early-AD: 13.0-15.9 years; n = 31) and late adolescents (Late-AD: 16.0-18.9 years; n = 60). INTERVENTION(S): History, physical examination, hormonal assays with the use of standardized protocols. MAIN OUTCOME MEASURE(S): Unadjusted and adjusted odds ratios (ORs; adjusted for body mass index [BMI] when applicable) were calculated for biochemical hyperandrogenism (HA), hirsutism (HIR), acne, and degree of oligo/amenorrhea (OA). PCOS phenotypes were classified as HIR+HA+OA, HA+OA, and HIR+OA. RESULT(S): Our analysis demonstrated minimal significant difference in the prevalence of the three PCOS phenotypes, or component features, between AD and YA patients. The risks for obesity were higher for YA versus AD, and the risk of acne was lower for YA versus AD. There was no significant difference between Early-AD and Late-AD. BMI-adjusted models did not significantly modify the main findings. CONCLUSION(S): The present study suggests that the PCOS phenotype is established in early adolescence, remains constant into adulthood, and is not related to BMI.

The Effects of Magnesium and Vitamin E Co-Supplementation on Hormonal Status and Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome.

Synergistic approach of magnesium and vitamin E may benefit clinical symptoms of patients with polycystic ovary syndrome (PCOS) through improving their metabolic profiles and reducing oxidative stress and inflammation. This study was designed to determine the effects of magnesium and vitamin E co-supplementation on hormonal status and biomarkers of inflammation and oxidative stress in women with PCOS. This randomized, double-blind, placebo-controlled trial was conducted among 60 women with PCOS, aged 18-40 years old. Participants were randomly divided into two groups to take 250 mg/day magnesium plus 400 mg/day vitamin E supplements or placebo (n = 30 each group) for 12 weeks. Fasting blood samples were taken at baseline and after the 12-week intervention to quantify related variables. Magnesium and vitamin E co-supplementation resulted in a significant reduction in hirsutism (ß - 0.37; 95% CI, - 0.70, - 0.05; P = 0.02) and serum high-sensitivity C-reactive protein (hs-CRP) (ß - 0.67 mg/L; 95% CI, - 1.20, - 0.14; P = 0.01), and a significant increase in plasma nitric oxide (NO) (ß 3.40 µmol/L; 95% CI, 1.46, 5.35; P = 0.001) and total antioxidant capacity (TAC) levels (ß 66.32 mmol/L; 95% CI, 43.80, 88.84; P < 0.001). Overall, magnesium and vitamin E co-supplementation for 12 weeks may benefit women with PCOS on hirsutism, serum hs-CRP, plasma NO, and TAC levels. Clinical trial registration number http://www.irct.ir : IRCT2017082733941N8.