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.

Spironolactone in dermatology: uses in acne and beyond.

Spironolactone is a synthetic aldosterone receptor antagonist, with a role off-label in various dermatological conditions. Its antiandrogenic properties make it suitable for diseases in which excess androgen production results in unwanted and psychologically distressing manifestations in susceptible females. Treatment with spironolactone aims to attenuate androgen-mediated conditions including acne, hidradenitis suppurativa, female pattern hair loss and hirsutism. We discuss the emerging utility of spironolactone in dermatology, its potential adverse effects and considerations for monitoring.

Prenatal Androgenization of Ewes as a Model of Hirsutism in Polycystic Ovary Syndrome.

The main clinical feature associated with hyperandrogenism in polycystic ovary syndrome (PCOS) in humans is hirsutism, where hair increases its length, pigmentation, and particularly its diameter. Currently, it is not known whether PCOS animal models also exhibit changes in the hair. Therefore, the aim of this study was to explore the wool characteristics in sheep prenatally androgenized (PA) with testosterone propionate. After 4 and 13 months of life, wool was collected from the top of the shoulder of both females and males (both androgenized and controls). The offspring sheep were followed for up to 19 months of life to evaluate testosterone and androstenedione serum levels by ultra-high-performance liquid chromatography-tandem mass spectrometry, determine insulin and glucose response to intravenous glucose tolerance test, and address estrus cyclicity during the second breeding season. PA male animals showed a reduction in wool fiber diameter at 4 months of age compared with controls (P = 0.02) but not at 13 months, whereas PA females showed increased hair diameter at 13 months (P = 0.002), with no difference at 4 months. No substantial changes in other hair parameters (length, color, and medullation) were identified. In addition, increased levels of serum testosterone were observed in PA female sheep compared with controls at 12 months (P = 0.03). Our results indicate for the first time, to our knowledge, that changes in wool fiber diameter observed in PA ewes replicate, at the translational level, the increase in hair diameter in hirsute women with PCOS.

The effect of CAG repeats length on differences in hirsutism among healthy Israeli women of different ethnicities.

PURPOSE: Variations in the degree of hirsutism among women of different ethnic backgrounds may stem from multiple etiologies. Shorter length of the polymorphic CAG repeats of the androgen receptor (AR) gene may be associated with increased activity of the receptor leading to hirsutism. We hypothesized that there are ethnic differences in the degree of hirsutism that is unrelated to androgen levels among Israeli women, and that the CAG repeats length may contribute to these differences. Anti-androgenic therapies, such as spironolactone, could be suggested if a shorter CAG repeats length is found to affect the difference in the degree of hirsutism between the ethnic groups. METHODS: Healthy Israeli Jewish women aged 18-45 years of Ashkenazi and non-Ashkenazi origin were invited to participate. Hirsutism was assessed using the simplified Ferriman-Gallwey (sFG) score, and serum total testosterone levels were measured as well. The CAG repeats length was determined by PCR. Methylation-sensitive methods were used to detect the fractional activity of each allele, and the weighted mean was calculated for the CAG repeats length. RESULTS: One-hundred and eight women were recruited (49 Ashkenazi and 59 non-Ashkenazi). The Ashkenazi women had a significantly lower degree of hirsutism (P<0.01), lower mean BMI (P = 0.003), total testosterone levels (P = 0.017), and longer weighted bi-allelic CAG repeats mean (P = 0.015) compared to non-Ashkenazi women. For the group as a whole, there was a significant negative correlation between the number of CAG repeats in the AR gene and the sFG score, while the number of repeats was not related to testosterone levels. Stepwise logistic regression revealed that ethnic origin and the CAG repeats length were the strongest factors affecting hirsutism (P<0.001, P = 0.03, respectively). CONCLUSIONS: There is a significant difference in the degree of hirsutism between Ashkenazi and non-Ashkenazi women in Israel that is partially explained by CAG repeats length.

In utero virilization secondary to a maternal Krukenberg tumor: case report and review of literature.

BACKGROUND: Krukenberg tumors are ovarian metastatic adenocarcinomas with a primary origin usually located in the stomach, colon, gallbladder, pancreas, or breast. Occasionally, these tumors produce virilization in the affected individual due to androgen production by luteinization of the tumoral stroma. It is believed that during pregnancy these tumors are more likely to increase androgen production due to the elevated levels of human chorionic gonadotropin (hCG). High maternal androgens can cross the placenta producing virilization of the female fetus. CASE PRESENTATION: A 46,XX newborn female, whose mother was diagnosed with a metastatic ovarian tumor during her second trimester of gestation associated with worsening hirsutism and acne, was found to have ambiguous genitalia at birth. Testosterone levels in both the mother and infant were elevated. Follow-up laboratory tests showed progressive normalization of circulating androgens after delivery. CONCLUSIONS: Krukenberg tumors are rare and may produce virilization of the mother and the female fetus when present during pregnancy.

[Dermatologic laser surgery].

In this article we give an overview of which skin conditions that are currently treated with laser and explains the basic principles of treatment. In addition, we summarize recommendations of the Danish Dermatological Society for demarcation of medical treatments which can be provided free of charge from cosmetic self-payment treatments.

The status of dermatoglyphics as a biomarker of Tel Hashomer camptodactyly syndrome: a review of the literature.

INTRODUCTION: Tel Hashomer camptodactyly syndrome is a rare disease and only a few cases have been reported. Dermatoglyphics potentially provide relevant phenotypic biomarkers that were initially noted as a vital clinical feature of this disease. Dermatoglyphics possibly can indicate growth disturbances that took place during early fetal development at the time when epidermal ridges were being formed into discernable patterns. Consequently, these intrauterine effects might well have occurred in association with the expression of the Tel Hashomer camptodactyly syndrome. Therefore, this review was undertaken to provide, as far as we know, the first attempt to broadly assess dermatoglyphic features that are connected with the Tel Hashomer camptodactyly syndrome. If a developmental association between dermatoglyphics and Tel Hashomer camptodactyly can be firmly established, this would probably document that Tel Hashomer camptodactyly disease has its origins during the early fetal period. METHODS: A systematic literature search was conducted using articles from PubMed (Medline), POPLINE, Trip Database, Cochrane Library, and gray literature up to 31 March 2015. The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: Fourteen relevant publications were included in the review. There were 23 cases of patients with Tel Hashomer camptodactyly syndrome that were described in these published articles. We reviewed the dermatoglyphics of 21 available cases out of all of the published and electronically available cases of Tel Hashomer camptodactyly. Eight cases reported whorls to be the most common digital pattern with an expected rise of ridge count. Two cases show significantly high frequencies of arch patterns. Further, there were increased numbers of palmar creases, along with abnormal flexion creases or other palmar dermatoglyphic abnormalities reported in all cases. CONCLUSION: This review highlighted the desirability of thoroughly observing and recording dermatoglyphic features when reporting on future patients with Tel Hashomer camptodactyly syndrome, in conjunction with carrying out modern molecular methods.

A novel insulin receptor mutation in an adolescent with acanthosis nigricans and hyperandrogenism.

Insulin receptor mutations cause extreme insulin resistance resulting in acanthosis nigricans and hyperandrogenism. We report a pre-menarchal adolescent female with normal weight, with severe acanthosis nigricans, acne, and hirsutism. Initial investigation revealed elevated fasting and post-prandial insulin and high testosterone and androstenedione levels. Her father had frequent complaints of hypoglycemia. Coding sequence and splice junction analysis of the INSR gene, in our patient and her father, revealed a heterozygous missense mutation in the ß subunit of the insulin receptor (Arg1131Trp), resulting in receptor loss of function. Metformin therapy and carbohydrate control improved acanthosis and menarche ensued within 3 months. Our case highlights the importance of distinguishing insulin resistance commonly associated with obesity from monogenic defects. Although, there is no consensus on treatment of children with monogenic forms of insulin resistance due to its rarity, dietary and lifestyle modifications and insulin-sensitizing agents play a key role in management.

Adjuvant eflornithine to maintain IPL-induced hair reduction in women with facial hirsutism: a randomized controlled trial.

BACKGROUND: Photoepilation is the treatment of choice for hair removal in patients with hirsutism, but it remains a challenge to prevent regrowth of hairs. OBJECTIVES: The objective of this study was to investigate whether topical eflornithine maintains hair reduction in hirsute patients after cessation of intense pulsed light (IPL) therapy. METHODS: A randomized, split-face, single-blinded controlled trial on topical eflornithine vs. no eflornithine treatment (control) after 5-6 IPL-treatments in 22 women with facial hirsutism. Application of eflornithine was initiated after the final IPL-treatment (baseline) and applied twice daily for 6 months to half of the face. Patients were assessed at baseline and 1, 3 and 6 months after the final IPL-treatment. The primary endpoint was difference in facial hair counts between eflornithine vs. no treatment. Secondary endpoints were patient-evaluated efficacy, patient satisfaction and safety. RESULTS: A total of 18 patients completed the study protocol. At 1 month after final IPL-treatment, eflornithine reduced hair regrowth by 14% (P = 0.007, n = 20 patients), at 3 months by 9% (P = 0.107, n = 19) and at 6 months by 17% (P = 0.048, n = 18) compared to no treatment. Patient-evaluated efficacy supported blinded hair counts and patients were satisfied with eflornithine treatment throughout the study (median VAS 5-6). Eflornithine was generally well tolerated, but blinded evaluation demonstrated deterioration of acne in two patients at final assessment. CONCLUSION: Topical eflornithine provides a self-administered treatment with a potential to maintain IPL-induced hair reduction in hirsute patients.

Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes.

Ablepharon macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are rare congenital ectodermal dysplasias characterized by similar clinical features. To establish the genetic basis of AMS and BSS, we performed extensive clinical phenotyping, whole exome and candidate gene sequencing, and functional validations. We identified a recurrent de novo mutation in TWIST2 in seven independent AMS-affected families, as well as another recurrent de novo mutation affecting the same amino acid in ten independent BSS-affected families. Moreover, a genotype-phenotype correlation was observed, because the two syndromes differed based solely upon the nature of the substituting amino acid: a lysine at TWIST2 residue 75 resulted in AMS, whereas a glutamine or alanine yielded BSS. TWIST2 encodes a basic helix-loop-helix transcription factor that regulates the development of mesenchymal tissues. All identified mutations fell in the basic domain of TWIST2 and altered the DNA-binding pattern of Flag-TWIST2 in HeLa cells. Comparison of wild-type and mutant TWIST2 expressed in zebrafish identified abnormal developmental phenotypes and widespread transcriptome changes. Our results suggest that autosomal-dominant TWIST2 mutations cause AMS or BSS by inducing protean effects on the transcription factor's DNA binding.

[RISK FACTORS AND CLINICAL PECULIARITIES OF SECONDARY OLIGOMENORRHEA IN ADOLESCENT GIRLS].

Risk factors related to secondary oligomenorrhea (SOM) are the presence of chronic extragenital pathology, abrupt changes in body mass during a short period of time, a burdened perinatal history at the onset of SOM after a year of regular menstruations. Adolescent girls with SOM differ from their healthy peers by a frequent occurrence of hirsutism, obesity and body mass deficit, uterine hypoplasia.

"Occult" ovarian Leydig cell tumor: when laboratory tells more than imaging.

Hyperandrogenism is a common finding in premenopausal age and is generally caused by polycystic ovarian syndrome or other benign disease. Androgen-secreting tumors represent only 0.2 % of the causes of hyperandrogenism and usually present with severe clinical features, abrupt onset, and very high androgens levels. We describe here three cases of occult ovarian Leydig cell tumors suspected on the basis of severe clinical features of hyperandrogenism rapidly worsening, with elevated serum total testosterone levels, in which bilateral ovariectomy was performed and tumor was confirmed by post-operative histology. In all three cases, imaging was negative for ovarian tumor. Moreover, in one case the confounding concomitant finding of bilateral adrenal masses posed an additional challenge. Our experience highlights that testosterone levels represent the most helpful marker in the diagnosis of androgen-secreting ovarian tumor. In the absence of imaging findings, bilateral ovariectomy should be indicated, if supported by unequivocal clinical and laboratory data.

Clinical, hormonal and metabolic characteristics of polycystic ovary syndrome among obese and nonobese women in the Croatian population.

Obesity has a deteriorating impact on women with PCOS, although prevalence and the impact of specific traits of PCOS remain inconstant in different populations. Therefore, the aim of this study was to explore the differences in clinical, hormonal and metabolic features between obese and nonobese Croatian women diagnosed as having PCOS according to Rotterdam consensus criteria. The study included 74 obese and 208 nonobese women with PCOS. Clinical, biochemical and metabolic variables were compared among those PCOS subgroups. Obese subjects with PCOS had a higher risk of developing oligo-amenorrhea (OR 3.7; 95% CI, 1.1-12.5) and lower risk for developing hirsutism and acne (OR 0.2; 95% CI, 0.1-0.3 and OR 0.8; 95% CI 0.5-1.4, respectively). Obese PCOS subjects also had a higher risk of developing hyperandrogenemia (OR 2.5; CI 95% 0.9-6.7), insulin resistance (OR 4.5; CI 95%, 2.6-7.9), hypercholesterolemia (OR 5.0, CI 95% 2.5-10.2), hypertriglyceridemia (OR 5.2; 95% CI, 2.9-9.2) as well as elevated serum CRP levels (OR 4.1; 95% CI 1.4-12.2) compared to nonobese PCOS women. In conclusion, nonobese Croatian women with PCOS are more inclined to cosmetic problems associated with PCOS then metabolic ones. This is the first study to report the impact of obesity on acne and irregular menses as a study outcome. Obesity deteriorates menstrual regularity, insulin sensitivity and lipid profile in Croatian women with PCOS; therefore one of the fundamental treatment strategies of PCOS should be obesity prevention.

Routine screening for Cushing's syndrome is not required in patients presenting with hirsutism.

CONTEXT: Prevalence of Cushing's syndrome (CS) in patients presenting with hirsutism is not well known. OBJECTIVE: Screening of CS in patients with hirsutism. SETTING: Referral hospital. PATIENTS AND OTHER PARTICIPANTS: This study was carried out on 105 patients who were admitted to the Endocrinology Department with the complaint of hirsutism. INTERVENTION: All the patients were evaluated with low-dose dexamethasone suppression test (LDDST) for CS. MAIN OUTCOME MEASURE: Response to LDDST in patients presenting with hirsutism. RESULTS: All the patients had suppressed cortisol levels following low-dose dexamethasone administration excluding CS. The etiology of hirsutism was polycystic ovary syndrome in 79%, idiopathic hirsutism in 13%, idiopathic hyperandrogenemia in 6%, and nonclassical congenital hyperplasia in 2% of the patients. CONCLUSION: Routine screening for CS in patients with a referral diagnosis of hirsutism is not required. For the time being, diagnostic tests for CS in hirsute patients should be limited to patients who have accompanying clinical stigmata of hypercortisolism.