Effectiveness and safety of tacrolimus with or without eltrombopag, as a part of immunosuppressive treatment of aplastic anemia in adults: a retrospective case series.

First-line treatment of aplastic anemia(AA) and for AA patients ineligible for hematopoietic stem cell transplantation (HSCT) has consisted of antithymocyte globulin (ATG), the calcineurin inhibitor cyclosporine A (CsA), and more recently eltrombopag. However, at our institution, we have successfully substituted another calcineurin inhibitor, tacrolimus, as a part of immunosuppressive threatment (IST) for AA due to more favorable toxicity profile. Since there is limited data on the use of tacrolimus in aplastic anemia, we conducted a retrospective review of twenty patients treated with tacrolimus-based immunosuppressive therapy (IST) as a first- or second-line treatment. The overall response rate was comparable to that of patients treated with CsA (18 patients). However, there were no cutaneous side effects observed in patients receiving tacrolimus, a relatively common finding with CsA use. Our data suggest that tacrolimus-based IST is a potential option in AA and might have a more favorable toxicity profile compared to CsA.

Evaluation of hirsutism and hormonal parameters in acne vulgaris patients treated with isotretinoin.

BACKGROUND: Although the effect of isotretinoin use on hormonal changes in acne pathogenesis is not fully known, there are limited studies on its effects on the development of hirsutism. In this study, it was aimed to evaluate the effect of isotretinoin use on hirsutism and hormonal parameters in patients with acne vulgaris. METHODS: In this study, 30 female acne patients and 30 healthy females were evaluated prospectively. Menstrual irregularity, LH, FSH, prolactin, progesterone, 17-OH progesterone, oestradiol, total testosterone, DHEA-S, insulin, glucose, TSH levels, Ferriman-Gallwey (FG) score and ultrasonography (USG) findings of control group and patient group were recorded. RESULTS: Pre-treatment progesterone (P = .007) and oestradiol (P = .001) levels of the patients were statistically lower than the control group. In the patient group, menstrual irregularity (P < 001) and FG hirsutism score at the third month of treatment were significantly higher than before treatment. In 10% of the patients, there were abnormal findings on pelvic USG in the third month of treatment. CONCLUSION: In our study, it could not be revealed that isotretinoin has a significant effect on pituitary, adrenal hormones and insulin resistance. We found that 3 months of isotretinoin treatment caused an increase in menstrual irregularity and FG hirsutism score.

Skin and hair abnormalities of Cantu syndrome: A congenital hypertrichosis due to a genetic alteration mimicking the pharmacological effect of minoxidil.

Cantu syndrome is an autosomal dominant disorder, first described by Cantu in 1982, that is characterized by congenital hypertrichosis, characteristic facial anomalies and cardiomegaly. Recent investigations have revealed that this syndrome is caused by mutations of ABCC9, which encodes a regulatory subunit of SUR2, an adenosine triphosphate-mediated potassium channel opener, expressed not only in smooth muscle but also in hair follicles. However, the abnormalities of skin and hair in patients with Cantu syndrome have not been well explored. We herein report three Japanese patients with Cantu syndrome and describe their specific skin manifestations and alterations in the histopathology of their hair follicles and sebaceous glands. Similar alterations were shared among those three patients and may be related to the function of SUR2, namely the regulation of hair follicle growth, because SUR2 is a known pharmacological target of minoxidil.

Medical and aesthetic procedural dermatology recommendations for transgender patients undergoing transition.

Transgender individuals may transition to their identified gender through social, hormonal, and procedural methods by using a multidisciplinary team of health care providers, including dermatologists. In this review, we discuss the medical and aesthetic dermatologic needs related to the transitioning of transgender patients and provide therapeutic and procedural recommendations. In addition to routine cutaneous conditions, dermatologists may need to treat hormonal therapy-related complications. Acumen for genital dermatology and familiarity with gender reassignment surgery is important for the dermatologist caring for a transgender patient. From a structural standpoint, transgender beauty poses a unique aesthetic task. We identify key differences in the facial structure and physique of males versus those of females. Dermatologists may have a tremendous impact on the lives of transgender individuals who seek to realize their gender identity.

Hair disorders in cancer survivors.

With increasing survival rates across all cancers, survivors represent a growing population that is frequently affected by persistent or permanent hair growth disorders as a result of systemic therapies, radiotherapy, surgical procedures, and therapeutic transplants. These hair disorders include persistent chemotherapy-induced alopecia, persistent radiotherapy-induced alopecia, endocrine therapy-induced alopecia and hirsutism, postsurgery alopecia and localized hypertrichosis, and persistent stem cell transplantation and targeted therapy-induced alopecia. The information contained in this continuing medical education series should facilitate a better understanding on hair disorders in cancer survivors so that adequate support and therapies may be provided.

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.

Tamoxifen-associated hirsutism: an unusual side effect in a 5-year-old girl with McCune-Albright syndrome.

Tamoxifen, a selective estrogen receptor modulator, has been used in the treatment of peripheral precocious puberty. A 5-year and 3-month-old girl, diagnosed with McCune-Albright syndrome, came in with abnormal hair growth approximately 2 months after the initiation of tamoxifen. The pattern of terminal hair on the skin following the administration of the drug and the exclusion of other causes suggested tamoxifen-induced hirsutism.

Systemic glucocorticoid therapy: risk factors for reported adverse events and beliefs about the drug. A cross-sectional online survey of 820 patients.

Despite systemic glucocorticoids are widely used, risk factors for most of their adverse events and patients' beliefs about the drug are poorly known. An online survey was conducted between February and July 2013 through the website www.cortisone-info.fr . Demographic (e.g., age, gender) and therapeutic (e.g., type of prescribed glucocorticoid, duration of prescription) data were collected. Patients were further asked to answer questions about glucocorticoid-induced adverse events and their beliefs about efficacy and safety of the drug. Risk factors for adverse events and efficacy/safety beliefs were assessed using multivariate logistic regression models. Eight hundred twenty questionnaires were analyzed (women 74.3 %; median age 49 [34-62] years, median equivalent prednisone dosage 20 [10-48] mg/day). The most frequently reported adverse events were insomnia (n = 477, 58.2 %), mood disturbances (n = 411, 50.1 %), hyperphagia (n = 402, 49.0 %), and lipodystrophy (n = 387, 47.2 %). The risk of some adverse events (e.g., weight gain, easy bruising) increased with the duration of exposure while other adverse events (e.g., insomnia, mood disorders, epigastric pain) were present since the first days of exposure. The risk of hirsutism, altered wound healing, mood disturbances, weight gain, lipodystrophy, hyperphagia, and epigastric pain decreased with age. Cutaneous disorders, morphological changes, and epigastric pain were more frequently reported by women. Interestingly, patients prescribed prednisolone reported less adverse events than those prescribed prednisone. No adverse event, demographical or prescribing characteristics were associated with beliefs about efficacy while factors associated with safety concerns were age (OR: 1.2 [1.1-1.3] per 10-year increase), osteoporosis (OR: 3.3 [1.4-7.9]), easy bruising (OR: 1.6 [1.1-2.3]), insomnia (OR: 1.7 [1.2-2.4]), and weight gain (OR: 1.6 [1.1-2.2]). These results may help clinicians to adapt information speech, therapeutic education, and clinical and laboratory monitoring of patients prescribed glucocorticoid therapy.

Short- and long-term clinical skin effects of testosterone treatment in trans men.

INTRODUCTION: Our knowledge concerning the effects of testosterone (T) therapy on the skin of trans men (female-to-male transsexuals) is scarce. AIM: The aim of this study was to evaluate the short- and long-term clinical effects of T treatment on the skin of trans men. METHODS: We conducted a prospective intervention study in 20 hormone naive trans men and a cross-sectional study in 50 trans men with an average of 10 years on T therapy. MAIN OUTCOME MEASURES: Acne lesions were assessed using the Gradual Acne Grading Scale, hair patterns using the Ferriman and Gallwey classification (F&G), and androgenetic alopecia using the Norwood Hamilton Scale. RESULTS: T treatment increased facial and body hair growth. The F&G score increased progressively from a median value of 0.5 at baseline to a value of 12 after 12 months of T administration. After long-term T treatment, all but one trans man achieved an F&G score indicative of hirsutism in women, with a median value of 24. Only one trans man acquired mild frontotemporal hair loss during the first year of T treatment, whereas 32.7% of trans men had mild frontotemporal hair loss and 31% had moderate to severe androgenetic alopecia after long-term T therapy. The presence and severity of acne increased during the first year of T therapy, and peaked at 6 months. After long-term T treatment, most participants had no or mild acne lesions (93.9%). Dermatological outcome was not demonstrably related to individual serum T or dihydrotestosterone levels. CONCLUSIONS: T treatment increased facial and body hair in a time-dependent manner. The prevalence and severity of acne in the majority of trans men peaked 6 months after beginning T therapy. Severe skin problems were absent after short- and long-term T treatment.

Tamoxifen-induced hirsutism.

Tamoxifen, a triphenylethylethylene, is an adjuvant therapy used for the treatment of oestrogen-receptor positive breast carcinoma due to its oestrogen receptor antagonist effect.1 We report here a case of rapid onset of hirsutism following administration of tamoxifen.

[Adverse effects of cyclosporin a observed in rheumatoid arthritis and psoriatic arthritis]. / Dzialania niepozadane w czasie leczenia cyklosporyna a u chorych na reumatoidalne i Luszczycowe zapalenie stawów-obserwacje wlasne.

INTRODUCTION: Rheumatoid arthritis (RA) and psoriatic arthritis (PA) represent diseases which often demand aggressive therapy in order to control the process and inhibit lesion formation in joints and organs. This kind of therapy can be achieved with cyclosporin A (CsA), particularly when combined with methotrexate (MTX). This combination is far more effective than single-drug therapy and is capable of significantly reducing the number of articular lesions. Considering the fact that monotherapy is associated with many adverse effects, it is feared that both drugs in combination may produce cumulative toxicity. The aim of this work was to determine the frequency of adverse effects caused by CsA in patients treated for RA and PA at the Outpatient Rheumatology Clinic of the First Public Hospital in Szczecin. MATERIAL AND METHODS: Our study group consisted of 61 patients, including 47 with RA--35 females, mean age 51 yrs (range: 21-69 yrs), mean disease duration 9.9 yrs (range: 2-23 yrs); 12 males, mean age 51.8 yrs (range: 33-74 yrs), mean disease duration 8 yrs (range: 3-14 yrs) and 14 with PA--6 females, mean age 41.1 yrs (range: 33-55 yrs), mean disease duration 7.8 yrs (range: 2-16 yrs); 8 males, mean age 42.9 yrs (range: 35-50 yrs), mean disease duration 7.0 yrs (range: 0.5-21 yrs). All patients were on MTX. During 11 years of follow-up, CsA was withdrawn due to adverse effects in 20 patients (32.8%). The following adverse effects were observed: arterial hypertension (n=19), hand tremor (n=11), hirsutism (n=7), elevated creatinine (n=17), gingival hypertrophy (n=9), abnormal appetite (n=2), peripheral neuropathy (n=1), lymphocytosis (n=1), skin lesions (n=1), diarrhea (n=2), recurrent infections (n=1), candidiasis (n=1), zoster (n=1), and neoplasm (n=2). Adverse effects responsible for withdrawal of CsA in 14 patients (23%) appeared more frequently during the first 12 months of therapy. Our observations indicate that CsA is well tolerated. The majority of adverse effects subsided after dose reduction or temporary withdrawal of the drug.

Testosterone for low libido in postmenopausal women not taking estrogen.

BACKGROUND: The efficacy and safety of testosterone treatment for hypoactive sexual desire disorder in postmenopausal women not receiving estrogen therapy are unknown. METHODS: We conducted a double-blind, placebo-controlled, 52-week trial in which 814 women with hypoactive sexual desire disorder were randomly assigned to receive a patch delivering 150 or 300 microg of testosterone per day or placebo. Efficacy was measured to week 24; safety was evaluated over a period of 52 weeks, with a subgroup of participants followed for an additional year. The primary end point was the change from baseline to week 24 in the 4-week frequency of satisfying sexual episodes. RESULTS: At 24 weeks, the increase in the 4-week frequency of satisfying sexual episodes was significantly greater in the group receiving 300 microg of testosterone per day than in the placebo group (an increase of 2.1 episodes vs. 0.7, P<0.001) but not in the group receiving 150 microg per day (1.2 episodes, P=0.11). As compared with placebo, both doses of testosterone were associated with significant increases in desire (300 microg per day, P<0.001; 150 microg per day, P=0.04) and decreases in distress (300 microg per day, P<0.001; 150 microg per day, P=0.04). The rate of androgenic adverse events - primarily unwanted hair growth - was higher in the group receiving 300 microg of testosterone per day than in the placebo group (30.0% vs. 23.1%). Breast cancer was diagnosed in four women who received testosterone (as compared with none who received placebo); one of the four received the diagnosis in the first 4 months of the study period, and one, in retrospect, had symptoms before undergoing randomization. CONCLUSIONS: In postmenopausal women not receiving estrogen therapy, treatment with a patch delivering 300 microg of testosterone per day resulted in a modest but meaningful improvement in sexual function. The long-term effects of testosterone, including effects on the breast, remain uncertain. (ClinicalTrials.gov number, NCT00131495.)

Seizure type, antiepileptic drugs, and reproductive endocrine dysfunction in Indian women with epilepsy: a cross-sectional study.

BACKGROUND: There is paucity of data regarding occurrence of reproductive endocrine disorders in Asian women with epilepsy (WWE) on antiepileptic drug (AED) therapy. PURPOSE: To determine the occurrence of reproductive endocrine disorders in Indian WWE, by seizure type and the AED use. METHODS: Consecutive 427 reproductive age WWE receiving various AEDs were screened for the occurrence of menstrual abnormalities, weight change, and hirsutism. Of these, 53 WWE with menstrual disturbances and/or hirsutism were further evaluated for ovarian morphology and reproductive hormonal profile. RESULTS: Menstrual abnormalities and/or hirsutism were observed in 83 of 427 (19.4%) WWE irrespective of epileptic seizure type; of these, 50 (60.2%) received valproate, 21 (25.3%) received carbamazepine, 11 (13.3%) received phenytoin, and one (1.2%) received phenobarbitone as the primary AED. Almost half of valproate-treated women had significant weight gain and obesity. Among 53 of 83 women evaluated further, 23.5% and 63.6% of valproate-treated women, 25% and 58.3% of carbamazepine-treated women, and none and 20% of phenytoin-treated women had polycystic ovaries (PCO) and hyperandrogenemia (HA), respectively. Valproate-treated women had significantly higher frequency of polycystic ovarian syndrome (PCOS) (11.8% vs. 2.5%, p < 0.0001) and mean serum testrosterone levels (1.78 vs. 1.36 ng/ml, p = 0.03), compared with women treated with other AEDs. LIMITATIONS: Limitations include small number of women in antiepileptic subgroups and a high drop out rate in women who underwent ultrasound and endocrinological investigations. CONCLUSION: Menstrual abnormalities, weight gain, obesity, and PCOS are frequent and significantly higher in WWE receiving valproate, independent of seizure type.

Sodium valproate, hyperandrogenism and altered ovarian function in Indian women with epilepsy: a prospective study.

PURPOSE: To assess the association of long-term sodium valproate therapy with reproductive endocrine disorders in Indian women with generalized epilepsy. METHODS: Clinical parameters, ovarian morphology, and serum reproductive hormone concentrations were evaluated in 30 clinically normal and eumenorrheic reproductive age women with generalized epilepsy who were newly initiated on valproate. Longitudinal evaluations were done in 25 of these women after 1 year, and in some of them after 2 and 3 years of therapy. RESULTS: Of the 25 women who completed 1 year follow-up, we observed clinically relevant weight gain in 40%, hirsutism in 20%, menstrual abnormalities in 24%, polycystic ovaries (PCO) in 16%, polycystic ovarian syndrome (PCOS) in 20%, and a significant increase in mean serum testosterone (p=0.046). A significant positive correlation existed between weight gain and the development of menstrual abnormalities (r=0.66, p<0.0001), hirsutism (r=0.53, p=0.006) and PCO (r=0.51, p=0.012). No correlation existed between weight change and serum reproductive hormonal changes. Yearly follow-up for next 2 years in some of these women revealed persistence of menstrual abnormalities, hirsutism and PCO, a significant linear increase in mean body weight, body mass index, and serum testosterone concentrations, and an increase in serum LH levels from second year onwards. LIMITATIONS: Limitations include small sample size and a high dropout rate on follow-up. CONCLUSIONS: Long-term valproate therapy in Indian women with generalized epilepsy is associated with development of hirsutism, significant weight gain, stable or progressive alterations in reproductive hormonal function, and ultimately a higher occurrence of PCOS.

13-cis-Retinoic acid (isotretinoin) unmasking of clinical polycystic ovary syndrome.

OBJECTIVE: To describe a woman in whom polycystic ovary syndrome manifested during treatment with 13-cis-retinoic acid (isotretinoin) for severe acne. METHODS: We present serial clinical and biochemical findings for a several month period before, during, and after therapy with 13-cis-retinoic acid. Homeostasis model assessment of insulin resistance was calculated from the fasting plasma glucose and insulin concentrations. RESULTS: A 32-year-old woman with some past features suggestive of metabolic syndrome took 13-cis-retinoic acid for 20 weeks as treatment of nodulocystic acne. During therapy, amenorrhea and hirsutism developed, as well as biochemical evidence of hyperandrogenemia and insulin resistance, as assessed by homeostasis model assessment of insulin resistance. After discontinuation of the medication, both the clinical features and the laboratory abnormalities resolved. CONCLUSION: 13-cis-Retinoic acid likely causes insulin resistance through its role as an agonist of retinoid A and X receptors. Although elevated levels of serum triglycerides are well documented with use of this drug, to the best of our knowledge this is the first report of a patient in whom polycystic ovary syndrome, a condition known to be associated with insulin resistance, manifested during isotretinoin therapy.

Longitudinal follow-up of reproductive and metabolic features of valproate-associated polycystic ovarian syndrome features: A preliminary report.

BACKGROUND: In the Systematic Treatment Enhancement Program for Bipolar Disorder, we showed that valproate is associated with new-onset menstrual-cycle irregularities and hyperandrogenism in 10.5% of 86 women. We now determine whether polycystic ovarian syndrome (PCOS) features reverse on valproate discontinutation. METHODS: Women with valproate-associated PCOS and those at risk for PCOS (valproate use < or =6 months) were re-evaluated for PCOS. RESULTS: Follow-up (mean 17 months) assessments were completed in 14 women (5 with treatment-emergent PCOS, 9 on valproate < or =6-month). Of seven women who developed valproate-associated PCOS, PCOS reproductive features remitted in three of four discontinuing valproate and persisted in all 3 continuing valproate. Menstrual-cycle irregularities improved among valproate-discontinuers whose PCOS features remitted (p = 0.01). There was a trend toward lower serum testosterone (p = 0.06). Body-weight and polycystic ovarian morphology did not change. CONCLUSIONS: In the first longitudinal bipolar-disorder study of valproate-associated PCOS, most valproate-discontinuers had improved reproductive features of PCOS despite static body-weight.

Drug-induced hirsutism.

Hirsutism is a symptom or sign, which may have more serious associations than cosmetic and psychological concern alone, such as adrenal hyperplasia and ovarian tumor, particularly if it develops well after puberty. Some medicines having androgenic activity may also cause this problem. Here, we present a case of a young unmarried girl who was given anabolic steroid for the treatment of dysmenorrhoea which resulted in hirsutism.

Rosiglitazone and ethinyl estradiol/cyproterone acetate as single and combined treatment of overweight women with polycystic ovary syndrome and insulin resistance.

BACKGROUND: Few studies have evaluated insulin sensitizers in comparison/association with oral contraceptives (OC) in women with polycystic ovary syndrome (PCOS) with insulin resistance (IR). This study assessed the effects of a thiazolidinedione versus an anti-androgenic estrogen-progestin followed by their sequential combinations in overweight PCOS women. METHODS AND RESULTS: Twenty-eight candidates in whom elevated insulin was not normalized after 4 months of diet were randomly assigned to 6 months of rosiglitazone 4 mg/day or to ethinyl estradiol 35 mg/cyproterone acetate 2 mg (EE/CPA: 21/28 days cycle). Each group then received both medications for another 6 months. Rosiglitazone reduced insulin, IR indices [homeostasis model assessment (HOMA) and quantitative sensitivity check index (QUICKI)] and the insulin area under the curve in response to an oral glucose tolerance test (OGTT), but had limited effect on lipids, androgens and hirsutism. EE/CPA did not modify insulin and OGTT response but increased high-density lipoprotein cholesterol and triglycerides and decreased androgens and hirsutism. Similar changes occurred during combined treatments. End results were highly significant in combined groups without noticeable side-effects or changes in safety parameters. CONCLUSIONS: In obese PCOS women with high insulin not corrected by diet, the combination of rosiglitazone and EE/CPA may be used to achieve complementary beneficial effects on endocrine-metabolic anomalies and clinical symptoms.