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.

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.

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.

[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.

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.

Clinical and biochemical characteristics of polycystic ovary syndrome in Croatian population.

Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting women of reproductive age. There are many typical signs and symptoms that allow for the diagnosis of PCOS depending on the criteria used. Interestingly, ethnicity influences the extent of these signs and symptoms; therefore, the frequency of symptoms varies between different countries and ethnic groups. The prevalence of this syndrome in Croatia is unknown, and it's clinical and biochemical characteristics have not yet been reported. During this study, we used the Rotterdam criteria to evaluate 365 Croatian women with PCOS, and compared them to 304 age matched controls to assess the clinical and biochemical abnormalities that occur in PCOS patients. The mean age of PCOS patients at presentation was 26.1 +/- 5.9 years and of controls were 28.0 +/- 4.2 years. Women with PCOS has significantly higher body mass index (BMI) than the control group, although in both groups most patients had normal weight (76.2% vs. 87.8%). Abdominal distribution of fat tissue was similar in both groups. Menstrual cycle abnormalities were observed in 90.7% of PCOS patients, and ultrasonographic appearance of polycystic ovaries was reported in 97.3% of PCOS cases. Nearly 75% of patients with PCOS had hirsutism and 49.6% had acne. We recorded significantly higher serum levels of luteinizing hormone (LH), total testosterone (TT), free testosterone (fT) and insulin, while the serum levels of sex hormone binding globuline (SHBG) and follicular stimulating hormone (FSH) were significantly lower than in the control group. Serum glucose values were not significantly different between the groups. In conclusion, chronic anovulation, hirsutism and ultrasound appearance of polycystic ovaries are the dominant features of PCOS in Croatian population. The majority of patients with PCOS had normal body weight. The incidence of insulin resistance in this group of patients is less than the previously described frequency in other populations of patients with PCOS and normal weight.

Zimmermann-Laband syndrome: a case report.

Zimmermann-Laband syndrome is a very rare disorder characterized by gingival fibromatosis, abnormalities of soft cartilages of the nose and/or ears, hypoplastic or absent nails and terminal phalanges, joint hypermobility, hypatoslenomegaly, mild hirsutism and learning difficulties. Early presentation of Zimmermann-Laband syndrome in a newborn has rarely been described. This paper describes a newborn patient with Zimmermann-Laband syndrome.

[Correlations between clinical signs and hormonal parameters in young women with hirsutism].

Hyperandrogenism is the pathological condition, which clinical signs are "androgendependent dermopathies" (seborrhea, acne, hirsutism, alopecia) and not in every cases evidence with hyperandrogenemia. Free testosterone is the most frequent marker of hyperandrogenism, but its determination routinely not feasible in all laboratories. Therefore, some models for calculating free and bioavailable testosterone have been developed. In women the testosterone sources are not only ovaries and adrenal glands, but also abdominal and peripheral fat. There are many investigations to definite correlations between body mass index, androgens and sex hormone binding globulin. The aim of this study was to define the correlations between clinical, biochemical markers of hyperandrogenism and body mass index, with regard of abdominal obesity in young women with hirsutism. 83 female adolescents (14-20 year) with hirsutism and 20 female adolescents in control group were included. C-peptide, estradiol, total testosterone, sex hormone binding globulin (SHBG) were measured. Free androgen index (FAI), free (cFT) and bioavailable (Bio-T) testosterone were calculated. The levels of C-peptide and glucose were used to compute Homa-IR (homeostasis model assessment for insulin resistance). There were detected significant high levels by all hormonal parameters of hyperandrogenism in women with hirsutism, than in control group. In patients with abdominal obesity were also found significant high levels by all calculated parameters of hyperandrogenism and significant low level of steroid-bind globulin, than in patients with central obesity. In two groups by hirsutism degree were not detected any differences between androgen markers. The findigs of this research suggest, that android obesity in female adolescents with hirsutism can cause harder hyperandrogenism and elevate free androgen index, free and bioavailable testosterone levels. The prophylactic reduction of body mass index may prevent complications.

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.

Two cases of isolated anterior cervical hypertrichosis.

Two unrelated Hispanic females, ages 4 and 3 years, respectively, each presented with a solitary patch of excessive terminal hair growth in the midline of the neck. This rare form of congenital localized hypertrichosis, known as anterior cervical hypertrichosis, is reported here as an isolated defect with no other underlying abnormalities.

Dyssegmental dysplasia in a South African neonate.

A female neonate born to nonconsanguineous Zulu parents had dyssegmental dysplasia, Silverman-Handmaker type. This condition has not previously been reported from the continent of Africa. She died at the age of 4 months following the development of pneumonia complicated by an unexplained anaemia.

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.

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.

[Leydig cell tumor as a cause of hirsutism in a postmenopausal woman]. / Androgenproduzierender Leydig-Zell-Tumor des Ovars als Ursache von Hirsutismus bei einer postmenopausalen Frau.

BACKGROUND: Hirsutism or virilization in postmenopausal women may be due to increased testosterone levels caused by an androgen-secreting tumor. The preoperative localization of small ovarian or adrenal androgen-secreting tumors is difficult. CASE REPORT: A 61-year-old, postmenopausal woman presented with progressive hirsutism and deepening of voice over the last 9 years. Serum testosterone was very high (almost 30 nmol/l). Computed tomographic (CT) scans of the adrenals and ultrasonography of the pelvis were negative. Selective catheterization and [(18)F]FDG-PET/CT investigation raised the suspicion of an androgen-secreting tumor of the right ovary. Oophorectomy was performed, and a Leydig cell tumor of the right ovary was confirmed on histological examination. CONCLUSION: Selective catheterization and [(18)F]FDG-PET investigation may aid the detection of androgen-secreting tumors.

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.