Characterization of polycystic ovary syndrome among Flo app users around the world.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex and multi-faceted endocrine disorder that affects 5-20% of women. Literature is limited regarding potentially differing PCOS phenotypes among women around the world. OBJECTIVE: To use Flo app technology to understand the multifaceted characteristics of PCOS across several countries and identify contributing risk factors to the development of this condition. STUDY DESIGN: Flo is a widely used female health and wellbeing app with period tracking functionality that provides a globally representative and medically unbiased perspective on PCOS symptomatology. A chatbot dialog on PCOS was subsequently administered on the Flo application (app) to users from 142 countries (with at least 100 respondents) who have the app running in English during September-October 2019. RESULTS: For analyses, we selected the five countries with the greatest number of respondents: US (n = 243,238), UK (n = 68,325), India (n = 40,092), Philippines (n = 35,131), and Australia (n = 29,926). Bloating was the most frequently reported symptom among PCOS-positive women and appeared to be the main predictor of PCOS in our model (odds ratio 3·76 [95% CI 3·60-3·94]; p < 0·0001). Additional top predictors of PCOS are high blood cholesterol and glucose levels. As BMI increased, the percentage of women who reported a physician-confirmed PCOS diagnosis also increased. However, women in India did not follow this trend. CONCLUSION: Our findings are based on the largest known PCOS dataset and indicate that symptoms are more complex than previously understood. The most frequently reported symptoms (bloating, facial hirsutism, irregular cycles, hyperpigmentation, and baldness) are broader than those included in the Rotterdam criteria. Future work should reevaluate and refine the criteria utilized in PCOS diagnosis.

Insulin resistance is associated with hirsutism in unselected reproductive-aged women.

OBJECTIVE: Hirsutism affects 5%-10% of reproductive-aged women worldwide and exhibits clinical importance as a cutaneous manifestation of underlying hyperandrogenism. Racial and genetic factors play roles in manifestation of hirsutism, and the prevalence of hirsutism seems to be low in East Asians. However, the reference value of the modified Ferriman-Gallwey (mFG) score to diagnose hirsutism and the prevalence of hirsutism have not been determined in Korean populations to date. We aimed to investigate the distribution of the mFG score and establish its reference value for defining hirsutism and to examine its relationship with metabolic and reproductive traits in reproductive-aged Korean women. DESIGN, PATIENTS AND MEASUREMENTS: We enrolled 2139 female volunteers of reproductive age (15-39 years). We recorded mFG scores from 0 to 4 on 9 different body locations (upper lip, chin, chest, arm, upper abdomen, lower abdomen, upper back, lower back and thighs). Hirsutism was defined as >95th percentile of mFG score. In addition, a 75-g oral glucose tolerance test was performed, and the homoeostasis model assessment of insulin resistance (HOMA-IR) was calculated. RESULTS: The mFG values of the 50th, 75th, 90th and 95th percentiles were 0, 1, 4 and 6, respectively. Therefore, the mFG score was indicative of hirsutism when the score was 6 or greater, which represents the 95th percentile. In the correlation analysis, total testosterone, free testosterone, fasting plasma insulin and HOMA-IR were positively correlated with mFG score (all Ps <0.05). Multiple linear regression analysis revealed that HOMA-IR (ß = 0.081) was positively associated with mFG score after adjustments for age, body mass index, total testosterone and the number of menses per year (P < 0.001). CONCLUSIONS: In conclusion, setting the 95th percentile of the mFG score as normal, the reference value to define hirsutism was 6 in reproductive-aged Korean women. HOMA-IR was positively associated with the mFG score even after adjustment for biochemical hyperandrogenism.

Androgens in women: Androgen-mediated skin disease and patient evaluation.

Androgens are produced throughout the body in steroid-producing organs, such as the adrenal glands and ovaries, and in other tissues, like the skin. Several androgens are found normally in women, including dehydroepiandrosterone, dehydroepiandrosterone-sulfate, testosterone, dihydrotestosterone, and androstenedione. These androgens are essential in the development of several common cutaneous conditions in women, including acne, hirsutism, and female pattern hair loss (FPHL)-androgen-mediated cutaneous disorders (AMCDs). However, the role of androgens in the pathophysiology of these diseases is complicated and incompletely understood. In the first article in this Continuing Medical Education series, we discuss the role of the skin in androgen production and the impact of androgens on the skin in women. Specifically, we review the necessary but insufficient role that androgens play in the development of acne, hirsutism, and FPHL in women. Dermatologists face the challenge of differentiating physiologic from pathologic presentations of AMCDs in women. There are currently no dermatology guidelines outlining the indications for endocrinologic evaluation in women presenting with acne, hirsutism, or FPHL. We review the available evidence regarding when to consider an endocrinologic workup in women presenting with AMCDs, including the appropriate type and timing of testing.

Androgens in women: Hormone-modulating therapies for skin disease.

Androgen-mediated cutaneous disorders (AMCDs) in women, including acne, hirsutism, and female pattern hair loss, can be treated with hormone-modulating therapies. In the second article in this Continuing Medical Education series, we discuss the hormone-modulating therapies available to dermatologists for the treatment of AMCDs, including combined oral contraceptives, spironolactone, finasteride, dutasteride, and flutamide. Available hormone-modulating treatments used for each AMCDs are reviewed, along with mechanisms of androgen modulation, safety profile, contraindications, monitoring parameters, and evidence of efficacy. Medications discussed include those that are approved by the US Food and Drug Administration for certain AMCDs and some that are used off-label. Despite the ubiquity of hormone-modulating therapies used for AMCDs, this review highlights the need for more rigorous studies to evaluate these therapies for acne, hirsutism, and female pattern hair loss.

New perspectives on the definition and management of polycystic ovary syndrome.

BACKGROUND: There is a growing debate on the opportunity of improving the understanding in the diagnosis and management of polycystic ovary syndrome (PCOS). OBJECTIVE: This review article summarizes recent research related to the definition of polycystic ovary syndrome (PCOS). METHODS: Review of the recent literature on the topic. RESULTS: New ideas on the definition of hyperandrogenism, based on new scientific data and clinical perspectives are presented. (i) In fact, recent studies have pointed out the need to improve the concept of androgen excess by using a larger androgen profile, rather than simply measuring the testosterone blood levels. (ii) Due to the poor correlation between androgen blood levels and the degree of hirsutism, it is proposed that the definition of hyperandrogenism should be based on the presence of blood androgen excess and hirsutism, considered separately, because their pathophysiological mechanisms may differ according to the different phenotypes of PCOS. (iii) The potential role of obesity in favoring the development of PCOS during adolescence is also discussed and the concept of "PCOS secondary to obesity" is developed. (iv) Finally, the need for greater appropriateness in the evaluation of possible coexistence is highlighted, in patients with PCOS who have fasting or glucose-stimulated very high insulin levels, or severe insulin-resistant states. CONCLUSIONS: Based on what was discussed in this review, we believe that there are margins for modifying some of the current criteria that define the various PCOS phenotypes.

Evaluation of insulin resistance in idiopathic hirsutism compared with polycystic ovary syndrome patients and healthy individuals.

INTRODUCTION: Hirsutism is defined as the excessive male-pattern growth of hair in women. Hirsutism is often idiopathic or the consequence of polycystic ovary syndrome (PCOS). Insulin resistance is common in PCOS (especially in obese patients) but the association between insulin resistance and idiopathic hirsutism (IH) is not clear. The aim of this study was to investigate the rate of insulin resistance in IH, compared with healthy individuals and patients with PCOS. METHODS: The study included three groups, patients with idiopathic hirsutism, PCOS and healthy women. Each group included 30 non-obese women. Fasting blood sugar (FBS), insulin level and insulin resistance (estimated by the homeostasis model assessment [HOMA-IRIR]) were compared in the three groups. RESULTS: There was a significant difference between the age of the women with IH compared with two other groups. There were no significant difference in levels of serum insulin (P = 0.49, HOMA-IR (P = 0.47) and prevalence of insulin resistance (P = 0.07) in the three groups. The age-adjusted prevalence of insulin resistance was similar in the three groups. CONCLUSION: Insulin resistance was no more frequent in IH patients than in healthy control groups.

Diagnostic features of polycystic ovary syndrome in adolescents (review).

The problem of Polycystic Ovary Syndrome (PCOS) is of a special importance due to its connection with not only medical but with psychosocial factors. PCOS is the most common endocrine cause of anovulatory infertility. It is a major factor for the metabolic syndrome, cardiovascular disease, type 2 diabetes mellitus (T2DM). Clinical symptoms of PCOS such as acne, hirsutism, obesity, alopecia represent psychological problem, especially for the adolescents. Many women who have PCOS have the onset of symptoms during adolescence. Early diagnosis and treatment of PCOS are important for preventing of the above mentioned long-term consequences associated with this condition. Adolescent patients often have diagnostic problems because the features of normal puberty are similar with symptoms of PCOS. This article reviews the diagnostic and differential diagnostic characteristics of PCOS in adolescents. In conclusion, consensus statement in adolescent patients is still awaiting. Our data suggest that it may be prudent to define adolescent PCOS according to the Carmina modified Rotterdam criteria. The increase rate of metabolic syndrome in adolescents with PCOS emphasize the importance of regular screening due to the high cardiometabolic disorders risk.

Urethra reconstruction with a prelaminated pedicled anterolateral thigh flap: a case report.

We present a case report of urethral reconstruction with a pedicled anterolateral thigh flap prelaminated with bladder mucosa in sex reassignment. The successful outcome may make this technique worthy to be considered in the secondary reconstruction of urethra in difficult cases. To the best of the authors' knowledge, no similar case has been previously described.

Peculiarities of sexual development and reproductive function in young women with childhood onset weight problems.

The risks of reproductive problems are higher in underweight and overweight or obese women, especially in case of rapid weight gain or loss. But evidence is inconsistent especially in relation to the effect of age of body weight changes. The aim of the study was detection of peculiarities of sexual development and reproductive function in underweight and overweight/obese females with childhood thinness or childhood obesity. 103 young females (48 - with low BMI, 55 - with high BMI) with different reproductive problems were examined prospectively. In all investigated patients full clinical examination was held, including body mass index (BMI), type of body fat distribution (waist-to-hip ratio), age of body weight changes, assessment of hirsutism, acne, stretch marks and hyperpigmentation, menstrual disturbances and fertility problems were recorded and gynecological ultrasound was performed. There was no difference established according to the age of menarche and types of menstrual disturbances between the groups of low BMI and high BMI females (p>.05). The correlation was established between the onset of menstrual disruption and progression of changes in body mass (R=.448, p=.005). Hirsutism, stretch marks and acantosis nigricans (hyperpigmentation) were exhibited significantly more frequently in the patients with high BMI (p<.05), whilst distribution of acne was almost the same in the study groups (p>.05). 74.5% of overweight and obese patients had upper body fat distribution (waist-to-hip ratio > 0.8), whilst underweight patients had mostly equal (66.7%) or lower body fat distribution (31.3%) (p=.000). Polycystic ovarian syndrome (PCOS) and metabolic syndrome (MS) was the most frequent in overweight and obese patients, whilst non-classical congenital adrenal hyperplasia (NCAH) and ovarian dysfunction prevailed in the underweight females (p<.05). Infertility was mostly observed in patients with high BMI (p<.05). In conclusion, the peculiarities of sexual development and menstrual function in young females with childhood thinness and obesity are related to their reproductive disorders, childhood BMI and progression of BMI changes.

Tel Hashomer camptodactyly syndrome: a case report.

Tel Hashomer camptodactyly syndrome (THCS) is a rare autosomal recessive camptodactyly with muscular involvement. The manifestations of THCS other than camptodactyly are clubbed feet, thenar and hypothenar hypoplasia, abnormal palmar creases and dermatoglyphic ridges, spina bifida and mitral valve prolapse. The syndrome was first described by Goodman et al in 1972 and thereafter two further cases with similar phenotype were seen. Herein, we present another case report and review of the literature of other syndromes associated with camptodactyly and mitral valve prolapse. Further cases with this syndrome need to be reported for mapping of the candidate loci. This will help in planning management and genetic counselling.

17-Hydroxysteroid dehydrogenase type 5 gene polymorphism (-71A/G HSD17B5 SNP) and treatment with oral contraceptive pills in PCOS women without metabolic comorbidities.

We studied (1) the effects of oral contraceptive pills (OCPs) on hirsutism, hormonal and metabolic variables in 49 polycystic ovary syndrome patients without metabolic comorbidities and (2) the effect of 17-hydroxysteroid dehydrogenase type 5 gene polymorphism (-71A/G HSD17B5 SNP) on the response to OCP treatment. Mean age was 21.9 ± 6.5 years. Patients received monophasic OCP (20 µg ethinyl estradiol plus 75 µg gestodene), 21/28 days per cycle, during 6 months; 32 patients with severe hirsutism also received spironolactone 100 mg. The frequencies of HSD17B5 genotypes were: AA = 0.49 (55.1%), AG = 0.42 (30.6%) and GG = 0.09 (14.3%). After 6 months, body mass index and waist circumference remained unchanged regardless of the presence of allele G. A slight reduction (p < 0.05) was noted in systolic blood pressure (p < 0.05) and luteinizing hormone levels, whereas a slight increase (p < 0.05) was noted in lipids. Total testosterone and hirsutism score declined, while sex hormone binding globulin increased after OCP treatment (p < 0.05). None of these changes were associated with genotype. Insulin and homeostasis model assessment remained unchanged after treatment and did not vary according to the presence of allele G. OCP seems to ameliorate androgenic symptoms without compromising metabolic parameters. The -71A/G SNP of HSD17B5 gene did not contribute to the improvements observed.

The investigation and management of hirsutism.

Excess male-pattern body hair in women is a very common and psychologically damaging condition. Although its cause is usually a chronic and benign disorder (most commonly polycystic ovary syndrome) it may rarely be an indication of a more serious endocrine disease such as Cushing syndrome or an androgen-secreting tumour. Investigations do not usually need to be extensive, but effective management is important, irrespective of cause, for what can be a debilitating symptom. Specific treatment of any underlying disease is important but in most cases treatment is empirical; it may simply involve physical hair removal, ideally by electrolysis or laser treatment. However, endocrine therapy to suppress androgen production and/or action is desirable in many, if not most, cases.

An update on the pathogenesis, inflammation, and metabolism in hirsutism and polycystic ovary syndrome.

Hirsutism is a common endocrine disorder, defined as increased growth of terminal hairs in a male pattern. Hirsutism is most often caused by polycystic ovary syndrome (PCOS), whereas only 5% patients are diagnosed with rare endocrine diseases. PCOS may be considered a multiorgan disease causing not only increased adrenal and ovarian sex hormone secretion but also changed secretion of gonadotrophins, growth hormone, and adrenocorticotrophic hormone (ACTH) from the pituitary. The majority of patients with PCOS are insulin resistant and PCOS is characterized by an increased inflammatory state with abdominal obesity and increased secretion of interleukins, chemokines, and adipokines. PCOS is therefore associated with an increased risk of the metabolic syndrome and type 2 diabetes (T2D). Patients with hirsutism present with increased bone mineral density despite decreased D-vitamin levels. The etiology to hirsutism and PCOS is most likely multifactorial including both genetic and environmental factors such as increased fetal stress and intrauterine growth retardation. In the present review, we give a comprehensive overview of the pathophysiology and multiple endocrine disturbances of hirsutism and PCOS.

Clinical, metabolic, and endocrine parameters in response to metformin and lifestyle intervention in women with polycystic ovary syndrome: a randomized, double-blind, and placebo control trial.

The aim of this study was to evaluate the effects of metformin in addition to diet and exercise on endocrine and metabolic disturbances in women with polycystic ovary syndrome (PCOS) in a prospective, double-blind, randomized, placebo (PBO) control trial. Thirty women with insulin resistance and PCOS received lifestyle modification and 1500 mg of metformin or placebo for 4 months. Before and after treatment, body mass index, waist/hip ratio, blood pressure, hirsutism, and menstrual patterns were evaluated. Serum concentrations of gonadotropins, androgens, progesterone, glucose, insulin, and lipids were measured. Lifestyle interventions resulted in similar weight and menstrual cycle's improvements in both groups. A significant reduction in serum fasting insulin, HOMA index, waist and testosterone levels was only observed with metformin. There were no significant changes in androstenedione, dehydroepiandrosterone sulfate, gonadotropins, and lipids levels. No other changes were observed in hirsutism or blood pressure. These findings suggest that metformin has an additive effect to diet and exercise to improve parameters of hyperandrogenism and insulin resistance. Although, a small decrease in body weight trough lifestyle changes could be enough to improve menstrual cycles in insulin-resistant women with PCOS.

[Hormones and hair growth]. / Hormone und Haarwachstum.

With respect to the relationship between hormones and hair growth, the role of androgens for androgenetic alopecia (AGA) and hirsutism is best acknowledged. Accordingly, therapeutic strategies that intervene in androgen metabolism have been successfully developed for treatment of these conditions. Clinical observations of hair conditions involving hormones beyond the androgen horizon have determined their role in regulation of hair growth: estrogens, prolactin, thyroid hormone, cortisone, growth hormone (GH), and melatonin. Primary GH resistance is characterized by thin hair, while acromegaly may cause hypertrichosis. Hyperprolactinemia may cause hair loss and hirsutism. Partial synchronization of the hair cycle in anagen during late pregnancy points to an estrogen effect, while aromatase inhibitors cause hair loss. Hair loss in a causal relationship to thyroid disorders is well documented. In contrast to AGA, senescent alopecia affects the hair in a diffuse manner. The question arises, whether the hypothesis that a causal relationship exists between the age-related reduction of circulating hormones and organ function also applies to hair and the aging of hair.

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.

Anti-androgenic therapy in young patients and its impact on intensity of hirsutism, acne, menstrual pain intensity and sexuality - a preliminary study.

OBJECTIVES: Using anti-androgenic contraception is one of the methods of birth control. It also has a significant, non-contraceptiveimpact on women's body. These drugs can be used in various endocrinological disorders, because of their abilityto reduce the level of male hormones.The aim of our study is to establish a correlation between taking different types of anti-androgenic drugs and intensity ofhirsutism, acne, menstrual pain intensity and sexuality. MATERIAL AND METHODS: 570 women in childbearing age that had been using oral contraception for at least three monthstook part in our research. We examined women and asked them about quality of life, health, direct causes and effects ofthat treatment, intensity of acne and menstrual pain before and after. Our research group has been divided according tothe type of gestagen contained in the contraceptive pill: dienogest, cyproterone, chlormadynone and drospirenone. Additionally,the control group consisted of women taking oral contraceptives without antiandrogenic component. RESULTS: The mean age of the studied group was 23 years ± 3.23. 225 of 570 women complained of hirsutism.The mean score for acne intensity before the use of contraception was 2.7 ± 1.34. The mean score for acne intensity after3 months of using contraception was 1.85 ± 1.02 (p < 0.001). 192 women reported excess hairiness in one or more areabefore treatment. Mean value based on Ferriman-Gallway scale before the treatment was 6.23 ± 6.21 and 5.39 ± 5.6 afterthe treatment (p < 0.001). CONCLUSIONS: All groups of drugs effectively reduced pain and acne severity. Cyproterone and drospirenone turned outas the most effective drugs in treating hirsutism. Surprisingly, according to our research, dienogest does not have anyimpact on body hairiness.

Role of hormones in pilosebaceous unit development.

Androgens are required for sexual hair and sebaceous gland development. However, pilosebaceous unit (PSU) growth and differentiation require the interaction of androgen with numerous other biological factors. The pattern of PSU responsiveness to androgen is determined in the embryo. Hair follicle growth involves close reciprocal epithelial-stromal interactions that recapitulate ontogeny; these interactions are necessary for optimal hair growth in culture. Peroxisome proliferator-activated receptors (PPARs) and retinoids have recently been found to specifically affect sebaceous cell growth and differentiation. Many other hormones such as GH, insulin-like growth factors, insulin, glucocorticoids, estrogen, and thyroid hormone play important roles in PSU growth and development. The biological and endocrinological basis of PSU development and the hormonal treatment of the PSU disorders hirsutism, acne vulgaris, and pattern alopecia are reviewed. Improved understanding of the multiplicity of factors involved in normal PSU growth and differentiation will be necessary to provide optimal treatment approaches for these disorders.

PCOS, sexuality, and clitoral vascularisation: a pilot study.

INTRODUCTION: In polycystic ovarian syndrome (PCOS) women, the changes in body appearance (mainly obesity and hirsutism) may influence the feminine identity of the patients with consequent depression and sexual disturbances. AIM: To evaluate if lean PCOS patients present an increased incidence of depression and sexual dysfunction in comparison with controls and if clitoral volume and vascularization are influenced by circulating androgens levels. METHODS: 25 lean PCOS women (Group I) and 18 healthy nonhirsute volunteers (Group II) were submitted, on day 3-5 of the cycle, to ultrasonographic and Doppler analyses, and to hormonal and biochemical evaluations. MAIN OUTCOME MEASURES: Utero-ovarian and clitoral ultrasonographic analysis, and color Doppler evaluation of the uterine, stromal ovarian, and dorsal clitoral arteries. Hormonal and nitrites/nitrates plasma concentrations were analyzed. Each woman filled in the 2-factor Italian McCoy female questionnaire (MFSQ) and the Beck's Depression Inventory questionnaire (BDI). RESULTS: Androgens resulted, as expected, more elevated in PCOS patients than in controls. However, the ultrasonographic (US) assessment of the clitoral body volume evidenced no significant differences between PCOS (0.72+/-0.41 mL) and control (0.62+/-0.20 mL) patients. The resistances registered at the level of the dorsal clitoral artery did not show any difference between Group I (PI=1.55+/-0.40) and Group II (PI=1.79+/-0.38). The 2-factor Italian MFSQ and the BDI did not show any difference between PCOS women and controls. CONCLUSIONS: In PCOS women, probably, the moderate hirsutism and hyperandrogenism do not induce the sense of loss of feminine identity and have no impact on sexual self-worth and sexual satisfaction.