Topical Testosterone Research Articles

PIH84 - Daily Dose and Costs Associated With Maintenance Therapy of Topical Testosterone Agents Among Hypogonadal Men

PIH84 59.24 mg and risk-adjusted dose PPPD was 113.3%, 113.5%, 126.4%, and 118.7% of RSD for Axiron, AndroGel 1% (non- significant vs. Axiron), AndroGel 1.62% (p<0.001 vs. Axiron), and Testim (p=0.047 vs. Axiron), respectively. Risk-adjusted third-party payer costs PPPD were $7.49, $9.49, $10.39, and $9.59 (all p<0.001 vs. Axiron), respectively. CONCLUSIONS: Maintenance dose as a proportion of RSD was the lowest among Axiron and AndroGel 1% patients, while third- party payer costs for the maintenance dose were lowest among Axiron patients. 14 (6.7%) 74 (12.1%) 35 (14.9%) 64 (11.5%) 0.0305 0.0059 0.0516 PPO 133 (63.6%) 364 (59.3%) 137 (58.3%) 219 (39.2%) 0.2664 0.2501 <0.0001 POS 34 (16.3%) 70 (11.4%) 31 (13.2%) 119 (21.3%) 0.0674 0.3600 0.1186 Other/unknown 28 (13.4%) 106 (17.3%) 32 (13.6%) 156 (28.0%) 0.1909 0.9461 <0.0001 HG b 201 (96.2%) 556 (90.6%) 220 (93.6%) 528 (94.6%) 0.0098 0.2253 0.3789 HG associated conditions c 16 (7.7%) 90 (14.7%) 31 (13.2%) 67 (12.0%) 0.0090 0.0584 0.0841 CCI, Mean (SD) 0.7 (1.2) 1.0 (2.0) 0.8 (1.4) 0.9 (1.9) 0.0736 0.4415 0.3124 Select comorbidities included in the CCI Renal disease 2 (1.0%) 19 (3.1%) 10 (4.3%) 21 (3.8%) 0.0905 0.0324 0.0424 HIV/AIDS 0 (0.0%) 12 (2.0%) 1 (0.4%) 12 (2.2%) 0.0438 1.0000 0.0434 Any testosterone use during baseline period d 113 (54.1%) 157 (25.6%) 57 (24.3%) 260 (46.6%) <0.0001 <0.0001 0.0653

Retrospective Analysis of Dose Titration and Serum Testosterone Level Assessments in Patients Treated With Topical Testosterone.

Patterns of care following topical testosterone agent (TTA) initiation are poorly understood. This study aimed to characterize care following TTA initiation and compare results between patients with and without a serum testosterone (T) assay within 30 days before and including TTA initiation. Adult men (N=4,146) initiating TTAs from January 1, 2011, to March 31, 2012, were identified from a commercially insured database. Patients were included if they initiated at recommended starting dose (RSD) and had ≥12 and ≥6 months of continuous eligibility preinitiation (baseline) and postinitiation (study period), respectively. Patients were stratified by preinitiation T assay. Maintenance dose attainment month was determined using unadjusted generalized estimating equations regression to compare dose relative to RSD month by month. Outcomes included maintenance dose attainment month, time to stopping of index TTA refills or a claim for nonindex testosterone replacement therapy (TRT), and proportion of patients with study period T assay or diagnosis of hypogonadism (HG) or another low testosterone condition, and were compared using chi-square and Wilcoxon rank-sum tests for categorical and continuous variables, respectively. Maintenance dose was attained in Month 4 postinitiation, at 115.2% of RSD. Approximately 46% of patients had a preinitiation T assay; these men were more likely to receive a diagnosis of HG or another low testosterone condition, to have a follow-up T assay, to continue treatment by filling a nonindex TRT, and less likely to stop refilling treatment with their index TTA. Differences in care following TTA initiation suggest that preinitiation T assays (i.e., guideline-based care) may be helpful in ensuring treatment benefits.

Application Site Affects the Pharmacokinetics of Topical Testosterone Applied to the Axilla Compared With the Inner Arm

PurposeThis study compared the pharmacokinetics of a single dose of 1% testosterone solution after application to the inner arm or the axilla as application sites for transdermal testosterone therapy. MethodsHealthy, not pregnant, premenopausal women, 18 to 45 years of age with a body mass index of 20 to 28 kg/m2 were enrolled into a single-center, open-label, randomized, 2-way crossover study. Serum total testosterone (TT), free testosterone (fT), and sex hormone binding globulin concentrations were measured. Pharmacokinetic parameters determined from serum TT and fT included area under the serum concentration versus time curve from time zero (pre-dose) until 72 hours post-dose (AUC0–72), Cmax, and Tmax. Descriptive statistics were performed on serum concentrations of TT and fT for each site. ANOVA was performed on AUC0–72 and Cmax. FindingsA single-dose application of 1% testosterone solution to the inner arm and the axilla produced clear increases in TT and fT. Slower and lower increases in TT and fT were observed after treatment to the inner arm. Based on baseline-corrected AUC versus time curves, the bioavailability of 1% testosterone solution was increased 2-fold for the axilla compared with the inner arm. ImplicationsThe absorption of a 1% testosterone solution was significantly greater after application to the axilla than to the inner arm. Study number DDS16; Australian Therapeutic Goods Administration, CTN 2005/158.

The impact of drug reimbursement policy on rates of testosterone replacement therapy among older men.

BackgroundDespite a lack of data describing the long-term efficacy and safety of testosterone replacement therapy (TRT), prescribing of testosterone to older men has increased with the availability of topical formulations. The magnitude of this increase and the impact of formulary restrictions on testosterone prescribing are poorly characterized.MethodsWe conducted a time series analysis using the linked health administrative records of men aged 66 years or older in Ontario, Canada between January 1, 1997 and March 31, 2012. We used interventional autoregressive integrated moving average models to examine the impact of a restrictive drug reimbursement policy on testosterone prescribing and examined the demographic profile of men initiating testosterone in the final 2 years of the study period.ResultsA total of 28,477 men were dispensed testosterone over the study period. Overall testosterone prescribing declined 27.9% in the 6 months following the implementation of the restriction policy (9.5 to 6.9 men per 1000 eligible; p<0.01). However, the overall decrease was temporary and testosterone use exceeded pre-policy levels by the end of the study period (11.0 men per 1000 eligible), largely driven by prescriptions for topical testosterone (4.8 men per 1000 eligible). Only 6.3% of men who initiated testosterone had a documented diagnosis of hypogonadism, the main criteria for TRT reimbursement according to the new policy.ConclusionGovernment-imposed restrictions did not influence long-term prescribing of testosterone to older men. By 2012, approximately 1 in every 90 men aged 66 or older was being treated with TRT, most with topical formulations.

Acceptability of a transdermal gel-based male hormonal contraceptive in a randomized controlled trial

ObjectiveFifty percent of pregnancies in the United States are unintended despite numerous contraceptive methods available to women. The only male contraceptive methods, vasectomy and condoms, are used by 10% and 16% of couples, respectively. Prior studies have shown efficacy of male hormonal contraceptives in development, but few have evaluated patient acceptability and potential use if commercially available. The objective of this study is to determine if a transdermal gel-based male hormonal contraceptive regimen, containing testosterone and Nestorone® gels, would be acceptable to study participants as a primary contraceptive method. Study DesignAs part of a three-arm, 6-month, double-blind, randomized controlled trial of testosterone and nestorone gels at two academic medical centers, subjects completed a questionnaire to assess the acceptability of the regimen. Of the 99 men randomized, 79 provided data for analysis. ResultsOverall, 56% (44/79) of men were satisfied or extremely satisfied with this gel-based method of contraception, and 51% (40/79) reported that they would recommend this method to others. One third of subjects (26/79) reported that they would use this as their primary method of contraception if it were commercially available today. However, men with concerns about sexually transmitted disease were significantly less satisfied than men without such concerns (p=0.03). ConclusionsA majority of the men who volunteered to participate in this trial of an experimental male hormonal contraceptive were satisfied with this transdermal male hormonal contraceptive. If commercially available, a combination of topical nesterone and testosterone gels could provide a reversible, effective method of contraception that is appealing to men. ImplicationsA substantial portion of men report they would use this transdermal male contraceptive regimen if commercially available. This method would provide a novel, reversible method of contraception for men, whose current choices are limited to condoms and vasectomy.

Efficacy of Vaginally Applied Estrogen, Testosterone, or Polyacrylic Acid on Sexual Function in Postmenopausal Women: A Randomized Controlled Trial

Female libido is multifactorial and complex. Declining estrogen levels in postmenopausal women affects vaginal function. The aim of this study was to evaluate female sexual function after using topical estrogen, testosterone, or polyacrylic acid as vaginal lubricants with K-Y jelly as a placebo lubricant. This was a randomized controlled clinical trial on 80 postmenopausal women between 40 and 70 years of age with follow-up at the Menopause Clinic of the CAISM Unicamp. The women were randomized to treatment with topical vaginal estrogen, testosterone, polyacrylic acid, or oil lubricant alone, three times a week for a period of 12 weeks from November 2011 to January 2013. We used the Female Sexual Function Index (FSFI) to assess changes in sexual response at baseline, and after 6 and 12 weeks. After 12 weeks of treatment, polyacrylic acid and topical testosterone produced improvements in the FSFI domains of sexual desire, lubrication, satisfaction, reduced pain during intercourse, and total score compared with lubricant alone. Treatment with topical estrogen in comparison with lubricant alone showed an improvement in the FSFI field of desire. The intragroup analysis over the time of the treatment showed improvements in the fields of desire, lubrication, and reduced pain for polyacrylic acid, testosterone, and estrogen. Furthermore, women who used testosterone showed improvements over time in the fields of arousal, orgasm, and satisfaction. Treatment of postmenopausal women with symptoms of vaginal atrophy with polyacrylic acid, testosterone, and estrogen for 12 weeks produced improvements in self-reported female sexual function when compared with a placebo lubricant.

Safety and Efficacy of Testosterone Replacement Therapy in Adolescents with Klinefelter Syndrome

We investigated the safety and tolerability of testosterone replacement therapy in adolescents with Klinefelter syndrome. We reviewed the medical records of all consecutive adolescents with Klinefelter syndrome evaluated between 2007 and 2012. Patients receiving testosterone replacement and aromatase inhibitor therapy were identified. Data on demographics, physical characteristics, medical history and serum hormone concentrations were collected for each patient. We evaluated longitudinal changes in serum testosterone, luteinizing hormone and follicle-stimulating hormone as well as changes in body mass index after the initiation of testosterone replacement therapy. We identified 151 adolescents with Klinefelter syndrome. Mean age at presentation was 11.6 years. Testosterone replacement therapy and aromatase inhibitors were initiated in 110 and 75 patients, respectively, at an average age of 13 to 14 years. Topical testosterone replacement therapy was used in 95% of patients with good clinical efficacy and compliance based on serial serum testosterone values. After the initiation of testosterone replacement therapy average serum testosterone improved from 240 to 650 ng/ml. Serum luteinizing hormone and follicle-stimulating hormone increased with the progression of puberty from 2.6 to 16.6 and 7 to 42 mIU/ml, respectively. No adverse outcomes related to testosterone replacement therapy were reported. Hormone supplementation with testosterone and aromatase inhibitors in adolescents with Klinefelter syndrome appears to be safe and effective for maintaining serum testosterone within the normal range. Compliance with topical formulations is high. Topical testosterone replacement therapy is not associated with the suppression of endogenous serum luteinizing hormone or follicle-stimulating hormone.

FSH Suppression Does Not Affect Bone Turnover in Eugonadal Men

In vitro and animal studies have reported conflicting results regarding an independent role for FSH in the regulation of bone turnover. Our objective was to test the hypothesis that suppressing serum FSH while holding serum gonadal steroid levels stable in the eugonadal range will affect biochemical markers of bone metabolism in healthy men. Eugonadal men aged 20 to 50 years participated in this randomized controlled trial at a tertiary care academic teaching hospital. Participants received monthly GnRH analog injections to suppress FSH secretion plus daily topical testosterone gel in prespecified doses (intervention group). Controls received matching placebos (control group). Subjects in the intervention group were individually matched with subjects in the control group to ensure that the mean testosterone and estradiol levels (measured every 4 weeks during the 16-week study period) in the 2 groups were similar. Biochemical markers of bone resorption (serum N-terminal telopeptide and C-terminal telopeptide), bone formation (serum osteocalcin), and FSH were measured at baseline and after 16 weeks of treatment. Serum FSH declined by 2% in the control group and by 60% in the intervention group (P < .0001 for the between-group difference). Despite the substantial suppression of serum FSH in the intervention group, serum N-terminal telopeptide, C-terminal telopeptide, and osteocalcin did not change in the intervention group, nor were any between-group differences observed. When gonadal steroid levels are held constant, short-to midterm suppression of FSH does not affect bone turnover in men. FSH does not appear to be a significant regulator of bone metabolism in eugonadal men.

Successful testicular sperm retrieval in adolescents with Klinefelter syndrome treated with at least 1year of topical testosterone and aromatase inhibitor

Successful testicular sperm retrieval in adolescents with Klinefelter syndrome treated with at least 1year of topical testosterone and aromatase inhibitor

Medication Adherence and Treatment Patterns for Hypogonadal Patients Treated with Topical Testosterone Therapy: A Retrospective Medical Claims Analysis

Medication Adherence and Treatment Patterns for Hypogonadal Patients Treated with Topical Testosterone Therapy: A Retrospective Medical Claims Analysis

Co‐occurrence of hemiscrotal agenesis with cutis marmorata telangiectatica congenita and hydronephrosis affecting the same side of the body

To our knowledge, there are nine previous reports of patients with congenital scrotal agenesis (CSA), seven of which were bilateral, and unilateral in two, also named as hemiscrotal agenesis (HSA). Here, we report a male infant with the previously undescribed co-occurrence of HSA with cutis marmorata telangiectatica congenita (CMTC), and hydronephrosis due to vesicoureteral reflux, all of them on the left side. CMTC is a segmental vascular malformation usually attributed to mosaicism of a postzygotic mutation, whereas the mechanisms in the CSA involve a failure on the labioscrotal fold (LSF) development due to a localized 5α-reductase deficiency and/or androgen insensitivity. Since the skin with HSA was affected also by CMTC and by the fact that it exhibited lack of response to the topical testosterone treatment, all this suggests to us an androgen insensitivity mosaicism in our patient restricted to the left LSF, because skin with intact androgen receptors normally shows some type of response. Since CSA and/or HSA have been also seen in patients with PHACES, popitleal pterygium syndrome, or as part of a recently proposed familial entity with CSA (or agenesis of labia majora as its female counterpart), developmental delay, visual impairment, and moderate hearing loss, further reports could confirm this manifest genetic heterogeneity, highly evocative of somatic mosaicism in our patient.

Hyperandrogenism secondary to topical testosterone exposure

Topical testosterone gels are now a widely used method of testosterone replacement therapy and have been shown to be convenient and effective[1]. The unintentional transfer of testosterone gel to children or partners by skin contact is a rare but significant adverse effect[2]. A 3-year-old well girl was referred for assessment of precocious puberty. Pubic hair had been first noted by her mother 9 months earlier. Examination revealed a tall girl (>99.9th centile) with no breast development but Tanner stage III pubic hair and cliteromegaly. Testosterone levels were elevated at 2.5nmol/l, as was her Androstenedione level at 1.1nmol/l. 17 OH P was normal and tumour markers were negative. Urine steroid profile was quantitatively normal but there was a modest increase in androgen metabolites. Bone age was advanced by 16 months. Ultrasound and MRI imaging of her ovaries and adrenals did not reveal a source of androgen production. Upon further direct questioning, her father revealed he was using topical testosterone replacement therapy. Her father was advised of measures to reduce secondary exposure. Her repeat testosterone level fell to <0.7 nmol/l upon retesting 4 months later and the cliteromegaly resolved. At follow up a further six months later, testosterone level had risen to 2.5nmol/l. Switching to the use of IM preparations was encouraged. Follow-up testing after these measures were adopted revealed normal undetectable testosterone levels (<0.7nmol/l). Once daily application of testosterone gels to the skin results in relatively stable and physiological testosterone levels in most users[3]. It is often favoured above the other methods of delivery of testosterone as it is painless, discrete and convenient to use. Even small quantities of transferred testosterone may result in clinical signs of hyperandrogenism. When reviewing children with evidence of virilization, we must remember to question parents about the potential for exogenous androgen exposure.

The Treatment of Vestibulodynia with Topical Estradiol and Testosterone

IntroductionCombined hormonal contraceptives (CHCs) use is becoming an increasingly recognized causes of vestibulodynia.AimThis study aims to describe pre- and posttreatment vestibular pain, sex hormone binding globulin (SHBG), and calculated free testosterone levels in women undergoing treatment for vestibulodynia.MethodsThis was a chart review of 50 premenopausal women who presented with vestibular pain while currently using CHCs. Pre- and posttreatment vestibular pain, SHBG, and calculated free testosterone levels were assessed.ResultsThere was a statistically significant improvement in posttreatment vestibular pain scores (P = 0.001), SHBG (P = 0.001), and calculated free testosterone (P = 0.001) levels from baseline.ConclusionWomen with vestibulodynia that began while on CHC may effectively be treated by discontinuing the CHC combined with the application topical hormone therapy. Symptomatic improvement is accompanied by normalization of calculated free testosterone and SHBG values. Burrows LJ and Goldstein AT. The treatment of vestibulodynia with topical estradiol and testosterone. Sex Med 2013;1:30–33.

Successful testicular sperm retrieval in adolescents with Klinefelter syndrome treated with at least 1 year of topical testosterone and aromatase inhibitor

To evaluate surgical sperm retrieval rates in adolescents with Klinefelter syndrome and testosterone replacement therapy (TRT). Case series. Academic medical center. Ten patients with Klinefelter syndrome, aged 14-22 years, treated with testosterone replacement and aromatase inhibitor therapy for a period of 1-5 years before surgical sperm retrieval. Microsurgical testis sperm extraction with cryopreservation of harvested tissue. Presence of spermatozoa within testis tissue. Successful sperm retrieval in 7/10 patients (70%). Use of topical TRT did not appear to suppress spermatogenesis in adolescents with KS. It is uncertain whether sperm retrieval rates would be higher or lower without testosterone replacement in these young males. Sperm cryopreservation should be discussed in all KS adolescents who are either receiving or considering initiating TRT.

Oral Enclomiphene Citrate Stimulates the Endogenous Production of Testosterone and Sperm Counts in Men with Low Testosterone: Comparison with Testosterone Gel

IntroductionClomiphene citrate is employed off‐label in men who have low testosterone and for the restoration of sperm counts in men who have used exogenous testosterone. Clomiphene is a mixture of two diastereoisomers: zuclomiphene and enclomiphene. We evaluated enclomiphene citrate in men with secondary hypogonadism. AimOur aim was to compare oral enclomiphene citrate as an alternative to topical testosterone. Main Outcome MeasuresBlood levels of total testosterone (TT), estradiol, follicle‐stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin, thyroid stimulation hormone, prolactin, and insulin‐like growth factor 1 IGF‐1 were measured at certain times after treatment with each agent. Sperm parameters were determined at the same visits. Free testosterone (FT) was calculated. MethodsThis was a proof‐of‐principle, randomized, open‐label, fixed dose, active‐control, two‐center phase IIB study in 12 men with secondary hypogonadism treated previously with topical testosterone. ResultsAfter discontinuation of topical testosterone, morning TT values averaged 165 ± 66 pg/dL. After 3 months, there was a significant rise in men receiving enclomiphene citrate and gel that was sustained for 3 months. At 6 months, TT levels were 545 ± 268 and 525 ± 256 pg/dL for groups receiving the gel and enclomiphene citrate, respectively. Only men in the enclomiphene citrate group demonstrated increased LH and FSH. TT decreased one month posttreatment to pretreatment values. Enclomiphene citrate elevated sperm counts in seven out of seven men at 3 months and six out of six men at 6 months with sperm concentrations in the 75–334 × 106/mL range. The gel was ineffective in raising sperm counts above 20 × 106/mL for all five men at 3 months and raised counts in only two or five men at 6 months. At follow‐up, only enclomiphene citrate treatment was associated with elevated sperm counts. ConclusionsEnclomiphene citrate increased testosterone and sperm counts. Concomitant changes in LH and FSH suggest normalization of endogenous testosterone production and restoration of sperm counts through the hypothalamic–pituitary–testicular axis.

Testosterone effect on brain metabolism in elderly patients with Alzheimer’s disease: comparing two cases at different disease stages

To describe the effect of testosterone replacement therapy (TRT) on the brain activity of two demented, hypogonadal male patients with early and late-stage Alzheimer's disease (AD), respectively. We describe the clinical and positron emission tomography (PET) findings for two individuals, one with early stage and the other with late-stage Alzheimer's disease, before and after treatment with a topical testosterone gel. Both patients were hypogonadal at baseline. We assessed cerebral glucose metabolism (CGM) via (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET). We investigated whether there are testosterone-susceptible areas within cerebral structures in patients with Alzheimer's disease. Under testosterone replacement therapy, changes in cerebral glucose metabolism were observed in both patients. Improvement in glucose uptake was observed most consistently in the parietal lobe and brainstem; decreased glucose metabolism was observed in the temporal lobe, the limbic system and the insula for these two subjects. These case reports demonstrate the potential for PET scanning to detect changes in cerebral glucose metabolism in hypogonadal men with Alzheimer's disease who are treated with testosterone. Further study will be needed to investigate the consistency and significance of these changes in terms of magnitude and brain region, and the correlation with functional changes.

Medication Adherence and Treatment Patterns for Hypogonadal Patients Treated with Topical Testosterone Therapy: A Retrospective Medical Claims Analysis

There is limited information on adherence to topical testosterone replacement therapy (TRT) among hypogonadal men. To determine adherence rates among men treated with topical testosterone gels and to examine factors that may influence adherence, including age, presence of a specific diagnosis, and index dose. Included were 15,435 hypogonadal men, from the Thomson Reuters MarketScan Database, who had an initial topical testosterone prescription in 2009 and who were followed for 12 months. Adherence to testosterone was measured by medication possession ratio (MPR), with high adherence defined as ≥0.8. Persistence was defined as the duration of therapy from the index date to the earliest of the following events: end date of the last prescription, date of the first gap of >30 days between prescriptions, or end of the study period (12 months). Adherence to topical TRT was low. By 6 months, only 34.7% of patients had continued on medication; at 12 months, only 15.4%. Adherence rates were numerically similar among men who received AndroGel or Testim topical gels and did not differ among men of different age groups. Approximately 80% of patients initiated at the recommended dose of 50 mg/day. Over time, an increased proportion of men used a higher dose. This change was the result of dose escalation, rather than of greater adherence among men initiating therapy at a high dose. Dose escalation was seen as early as 1 month into therapy. Approximately 50% of men who discontinued treatment resumed therapy; most men used the same medication and dose. Discontinuation rates are high among hypogonadal men treated with testosterone gels, irrespective of their age, diagnosis, and index dose. Further study, evaluating other measurable factors associated with low adherence among patients receiving topical TRT, may lead to interventions designed to improve adherence with therapy.

Abstract 1326: Oral enclomiphene citrate lowers IGF-1 in men with secondary hypogonadism while raising testosterone: Implications for cancer prevention.

Abstract Introduction: Lowered hGH and IGF-1 have been linked with protection from various cancers. Methods and Subjects: We determined levels of IGF-1 and pituitary hormones in men with secondary hypogonadism under treatment with enclomiphene (a.k.a. Androxal) in comparison to topical testosterone (T) or placebo. Three, randomized, blinded, phase II studies evaluating daily oral Androxal were performed: ZA-201 investigated 12 men taking 25mg of Androxal in comparison to a gel for 6 months, ZA-202 enrolled 119 diabetic men taking 12.5 or 25 mg Androxal versus placebo for 3 months, and ZA-204 investigated 47 men taking 6.25mg, 12.5mg and 25mg Androxal versus another gel for 6 weeks. All subjects had initial total T &amp;lt;350 ng/dL and low-to-normal LH (&amp;lt;12 IU/L). Serum samples were taken for T, LH and FSH before and after dosing. We could not measure hGH directly but measured its marker, liver-produced IGF-1. Results: All treatments raised T into the normal range (300-1000 ng/dL), but placebo did not in ZA-202. Androxal elevated LH and FSH. Gels decreased LH and FSH strongly. Unexpected was the strong action of Androxal to lower serum IGF-1 in all three trials. Both Androxal and topicals lowered serum IGF-1 but Androxal was more effective. An example is given from ZA-204 below. Dose groups showed no differences in IGF-1 before (p = 0.94) but significance after treatment (p = 0.03), Conclusions: Endocrine profile indicate that enclomiphene citrate stimulates the pituitary, resulting in increased LH and FSH and eventually T. The results on IGF-1 cannot be attributed to T since topicals, when used, raised T but not IGF-1 whereas only enclomiphene citrate raised T but lowered IGF-1. Enclomiphene citrate is different from topicals and may be a new way to relieve low T in men with an intact hypothalamus-pituitary-testicular axis. If Androxal can lower hGH or IGF-1 in aging men at risk for prostate cancer, its use in men with secondary hypogonadism is an important new treatment. Effect of Treatment on IGF-1 dose subjects IGF-1 (SD)before IGF-1 (SD) after Versus Gel MMW 6.25mg 12 101 (43) 54 (30) p&amp;lt;0.01 12.5mg 10 94 (47) 50 (24) p&amp;lt;0.005 25mg 12 96 (45) 62 (42) p&amp;lt;0.01 Gel 13 103 (46) 90 (34) Citation Format: Ronald D. Wiehle, Gregory K. Fontenot. Oral enclomiphene citrate lowers IGF-1 in men with secondary hypogonadism while raising testosterone: Implications for cancer prevention. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1326. doi:10.1158/1538-7445.AM2013-1326

LÍQUEN ESCLEROSO DA VULVA – REVISÃO DE 208 CASOS

Introdução: O líquen escleroso (LE) é uma dermatose inflamatória crónica idiopática com predilecção ano- genital, sendo mais comum na mulher no período pós-menopausa. Objectivos: Análise retrospectiva dos casos de LE vulvar diagnosticados e tratados na consulta de Patologia Vulvar, entre 1986 e 2004. Material e Métodos: Um total de 208 caucasianas foi incluído no estudo. Foram consultados processos clínicos e realizado estudo estatístico das variáveis idade, localização, sintomas e sinais clínicos, associação com outras patologias, tratamento, follow-up e complicações. Resultados: A duração média do LE foi de 6,3 anos. A idade média das mulheres à data do diagnóstico foi de 59,6 anos e à data do desenvolvimento dos sintomas de 53 anos. Cento e oitenta e duas (87,5%) encontravam-se no período pós-menopausa. O prurido foi o sintoma predominante (90,9%). Apenas 39 (18,8%) doentes não apresentavam atrofia vulvar e 142 (68,2%) não tinham envolvimento do intróito vaginal. O exame histológico confirmou LE em 185 (93,9%) e foi compatível nos restantes 12 (6,1%). O propionato de testosterona (PT) foi utilizado em 88 (42,3%) casos, os corticói- des tópicos em 24 (11,5%) e ambos em 76 (36,6%). O follow-up médio foi de 9,5 anos. Nove (4,3%) mulheres desenvol- veram CEC vulvar, sendo a idade média das mesmas ao diagnóstico de 68,2 anos. Conclusões: O LE predominou no período pós-menopausa. O prurido e atrofia vulvar foram os achados clínicos mais frequentes. A maior parte dos casos foi confirmado por histologia. O PT tópico foi a arma terapêutica mais usada. A malignização ocorreu em nove casos.PALAVRAS-CHAVE – Vulva; Líquen Escleroso; Propionato de Testosterona; Corticóides; Carcinoma Espinocelular.

Virilization in two pre-pubertal children exposed to topical androgen

Androgen replacement therapy for male hypogonadism may be prescribed utilizing intramuscular, oral or more recently, topical formulations. With topical formulations, there is a risk of person-to-person transmission if appropriate precautions are not taken. We describe two cases of virilization in pre-pubertal children following passive transfer of paternal topical testosterone. A 21 month old male was referred with a 6 week history of pubic hair, phallic growth, and linear growth spurt. Genital examination revealed Tanner stage 2 pubic hair and Tanner stage 3 phallic development, which was discordant with the pre-pubertal testicular size (2 mL bilaterally). A 3 year 8 month old girl was referred for a 2 month history of increasing pubic hair development. Examination revealed Tanner stage 2 pubic hair and Tanner stage 1 breast development. Both of these patients had fathers who had been diagnosed with hypogonadism and were being treated with topical androgen gel therapy, which they applied to their arms and chest before bed. In addition, both patients often slept with their parents resulting in skin-to-skin contact. Investigations were consistent with gonadotropin independent virilization with both patients demonstrating elevated testosterone levels. Testosterone levels returned to normal pre-pubertal levels with no further development of secondary sexual characteristics following discontinuation of exposure to topical testosterone. Precautions must be taken to prevent person-to-person transfer of topical steroids. With the increasing popularity of topical steroids for the treatment of low testosterone, it is imperative that these therapies be prescribed and utilized judiciously to prevent harm, specifically gonadotropin-independent virilization.