Is There an Association between 5a Reductase Inhibitors and Metabolic Syndrome? A Narrative Review of the Literature.

Finasteride and dutasteride are 5a Reductase Inhibitors (5a-RIs) and comprise the mainstay of treatment for the management of patients with benign prostatic hyperplasia. 5a-RIs are expressed in a variety of tissues, such as adipose tissues and liver, resulting in a reduction of glucocorticoid levels and affecting androgen regulation and metabolic function. As a result, the administration of these regimens may generate adverse metabolic events, such as liver disease, hyperglycemia, hyperlipidemia, and diabetes mellitus. Although several studies have tried to record these adverse metabolic events both in human subjects and animal models, the exact mechanisms of these actions have not been well described yet in the literature. Further well-designed clinical trials are needed to elucidate the exact role of 5a reductase inhibitors in the progression of the metabolic syndrome. The aim of this study was to systematically review the literature concerning the role of dutasteride or finasteride in the progression of metabolic adverse events and further investigate possible pathophysiologic mechanisms.

Poseidon and Caeneus: a case of pubertal gender inversion in Greek mythology.

Disorders of sex development (DSDs) are very frequently encountered in ancient Greek mythology. One of the most striking types of DSD described in many myths is gender transformation wherein a female becomes a male or vice versa. Herein, we present via the marvelous myth of Poseidon and Caeneus a case of pubertal gender inversion. A medical interpretation of the myth whereby we attempt to form a diagnosis of this case of DSD is also presented.

Novel Deleterious Mutation in Steroid-5α-Reductase-2 in 46, XY Disorders of Sex Development: Case Report Study.

Background: Steroid-5α-reductase-2 (SRD5A2) and 17ß-hydroxysteroid dehydrogenase type 3 (17ß-HSD3) enzyme deficiencies are frequent causes of 46, XY disorder of sex development (46, XY DSD), where an infant with 46, XY has a female phenotype. We assessed the hydroxy-steroid-17ß-dehydrogenase-3 (HSD17B3)and SRD5A2 genes in twenty Iranian phenotypic females with 46,XY DSD. Materials and methods: All exons in HSD17B3 and SRD5A2 genes were subjected to PCR amplification followed by sequencing. Results: Of 20 identified 46, XY DSD patients, one had a homozygous missense 17ß-HSD3 mutation Ser65Leu (c.194C > T). We found 1 SRD5A2 novel homozygous missense mutation of Tyr242Asp (c.891T > G) in exon 5, which in-silico analyses revealed that this mutation may have deleterious impact on ligand binding site of SRD5A2 protein. Three other individuals harbored 17ß-HSD3 deficiencies without identified mutations. Conclusions: SRD5A2 and 17ß-HSD3 mutations are found in 10% of 46, XY DSD Iranian patients.

Leucippus, either male or death: a case of sex reversal by divine intervention.

The concept of metamorphosis (change of form, structure, or substance) is very frequently encountered in Ancient Greek and Roman literature. One of the most striking types of metamorphosis described in many myths is gender transformation, where a man becomes a woman or vice versa. Herein, we present a case of pubertal gender inversion, the marvelous story of the Cretan Leucippus, which not only inspired many ancient writers but also led to the development of a distinct, local, religious cult. A medical interpretation of the myth, whereby we attempt to establish a diagnosis for this case of heterosexual puberty, is also provided.

"Congruency the ART of Being Real" - 46XY DSD Due to 5 α Reductase Deficiency - Challenges in Decision Making.

Disorders of sexual development (DSDs) are heterogenous group of disorders characterized by discrepancy in chromosomal, gonadal, and phenotypic sex. DSD is a Medico-Social Emergency. 5 α reductase type 2 deficiency is one of the rare causes of 46 XY DSD. The degree of under virilization varies from clinically female to a near male phenotype. Müllerian structures were absent. At puberty, there might be features of virilization. Gender incongruence or dysphoria occurs frequently during puberty. An important marker for diagnosis is an elevated testosterone to dihydrotestosterone ratio in the basal state or following HCG stimulation. All 46 XY DSD require an appropriate molecular diagnosis prior to gender assignment and gender reassignment surgery. Gender reassignment surgery and/or Gonadectomy should be performed only after 18 years if there are compelling indications like suspicion of malignancy or presence of gender dysphoria or gender incongruence.

Skin steroidogenesis in health and disease.

The skin is an important extra-gonadal steroidogenic organ, capable of metabolizing various hormones from their precursors, as well as of synthesizing de novo a broad palette of sex steroids and glucocorticoids from cholesterol. In this manuscript, we review the major steroidogenic properties of human skin and we suggest steroidogenesis' impairment as a cardinal factor for various pathological conditions such as acne, rosacea, atopic dermatitis, and androgenic alopecia.

Urinary Prostate Cancer Antigen 3 as a Tumour Marker: Biochemical and Clinical Aspects.

Due to low specificity of Prostate-Specific Antigen (PSA) we face a certain risk of overdiagnosis and overtreatment of Prostate Cancer (PCa). The benefits and harms of PSA-screening are controversially discussed. To overcome this weakness of PSA novel PCa biomarkers and detection tools are required.The urine-based biomarker Prostate Cancer Antigen 3 (PCA3) has been shown to be highly PCa-specific. Application of PCA3 was tested in the diagnostic setting and staging. Several studies pointed out the additional value of PCA3 for further stratification of men selected for biopsy (BX) based on an elevated PSA and/or an abnormal digital rectal examination (DRE). Its combined use with established clinical risk factors for positive prostate BX, particularly within nomograms or risk calculators, may represent a valid and helpful aid for clinicians in patient counselling and BX indication confirmation.When it comes to prediction of favourable or unfavourable histopathological features, respectively, such as tumour volume or PCa significance, PCA3's value remains controversial. Based on relatively small patient numbers, PCA3 has been identified to independently predict small-volume and insignificant PCa. However, in other studies PCA3 was not associated with advanced disease and its ability of predicting PCa aggressiveness in men undergoing radical prostatectomy is limited.PCA3's value may be best given for BX outcome prediction. Finally, the implementation of the PCA3 promoter in developing new highly PCa-specific gene therapies represents a promising perspective in the near future.

Eficacia de un complemento alimenticio con serenoa serrulata y tocotrienol-tocoferol frente a la alopecia androgenética y el efluvio telógeno femeninos: A propósito de un estudio piloto / Effectiveness of a dietary supplement with serenoa serrulata and tocotrienol-tocopherol against female androgenetic alopecia and telogen effluvium: Report of a pilot study

Introducción: la alopecia androgenética femenina (FAGA) y el efluvio telógeno (ET), son causas comunes de pérdida de cabello en las mujeres. Un hecho conocido en estos tipos de alopecia es la mayor actividad de la 5α-reductasa, que reduce la testosterona a dihidro-testosterona, andrógeno que acelera el ciclo capilar y acorta su duración. La Serenoa serrulata es una especie vegetal, cuyos componentes presentan un efecto inhibidor de la 5α-reductasa. Objetivo: el objetivo principal de este estudio, consistió en valorar la eficacia y la tolerancia, frente a la alopecia femenina de la administración diaria oral, de un complemento alimenticio con extracto de Serenoa serrulata, L-cistina, complejo tocotrienol-tocoferol, hierro, zinc y vitaminas H, B1, B2, B3, B5, B6 y B12 durante seis meses. Material y Método: estudio piloto unicéntrico, abierto, no aleatorizado, a simple ciego, de 180 días de duración, llevado a cabo en voluntarias con FAGA o ET. Se valoró el aspecto macroscópico del cabello, la densidad capilar mediante microfotografía, la relación anágena / telógena (A/T) mediante tricograma, el número de cabellos desprendidos mediante ensayos de peinado ("combing test") y de lavado ("wash test"). Se realizó una encuesta de autovaloración de los resultados. Resultados: la edad media de las participantes (n=10) fue de 40±15,5 años. El tiempo de evolución fue de 4,5±2 años y de tres meses para la FAGA y el ET, respectivamente. Al final del tratamiento las participantes presentaron un incremento medio del 6,9%, en la proporción de cabellos en fase anágena y la relación A/T media aumentó a 3,3. El 80% mostraron una mayor densidad capilar al finalizar el estudio. Al cabo de tres meses, todas las participantes presentaron una reducción media de la pérdida de cabellos del 56%, respecto de la visita basal. El 90% percibieron una mayor o igual cantidad de cabello al final del estudio y el 80% lo notaron más fuerte. No se registró ninguna molestia inducida por el tratamiento. Conclusiones: la buena evolución de las variables analizadas apunta a un beneficio terapéutico, frente a la FAGA y el ET. Estudios con mayor número de pacientes, son necesarios a futuro.

Introduction: female androgenetic alopecia (FAGA) and telogen effluvium (TE) are common causes of hair loss in women. A known fact in these types of alopecia is the increased activity of 5a-reductase which reduces testosterone to dihydrotestosterone, accelerating hair cycle and shortening its duration. Serenoa serrulata is a plant species whose components have an inhibitory effect on 5a reductase. Objective: the main objective of this study was to evaluate the efficacy and tolerance against female alopecia of a food supplement with Serenoa serrulata extract, L-cystine, tocotrienol-tocopherol complex, iron, zinc, and vitamins H, B1, B2, B3, B5, B6 and B12 administered daily for six months. Material and Methods: single-center, open-label, non-randomized, single-blind, 180-days pilot study conducted in women with FAGA or TE. The study assessed the macroscopic appearance of the hair, hair density by microphotograph, the anagen / telogen ratio (A/T) by trichogram, and the number of detached hair by combing and wash tests. Self-assessment survey of the results was performed. Results: the mean age of participants (n = 10) was 40 ± 15.5 years. FAGA and ET had an evolution of 4.5 ± two years and three months, respectively. After treatment the participants had an average increase of 6.9% in the proportion of hairs in anagen phase, and the mean A/T ratio increased to 3.3. Eighty percent or patients showed an increased capillary density at study end. After three months, all participants had a mean reduction of hair loss of 56% vs baseline. Ninety percent perceived a greater or equal amount of hair at the end of the study and 80% noticed it stronger. No adverse effects induced by treatment were observed. Conclusions: the good results of the analyzed variables suggest a therapeutic benefit against FAGA and ET. Additional research is warranted to confirm the observed data.

Eficacia de un complemento alimenticio con serenoa serrulata y tocotrienol-tocoferol frente a la alopecia androgenética y el efluvio telógeno femeninos: A propósito de un estudio piloto / Effectiveness of a dietary supplement with serenoa serrulata and tocotrienol-tocopherol against female androgenetic alopecia and telogen effluvium: Report of a pilot study

Introducción: la alopecia androgenética femenina (FAGA) y el efluvio telógeno (ET), son causas comunes de pérdida de cabello en las mujeres. Un hecho conocido en estos tipos de alopecia es la mayor actividad de la 5α-reductasa, que reduce la testosterona a dihidro-testosterona, andrógeno que acelera el ciclo capilar y acorta su duración. La Serenoa serrulata es una especie vegetal, cuyos componentes presentan un efecto inhibidor de la 5α-reductasa. Objetivo: el objetivo principal de este estudio, consistió en valorar la eficacia y la tolerancia, frente a la alopecia femenina de la administración diaria oral, de un complemento alimenticio con extracto de Serenoa serrulata, L-cistina, complejo tocotrienol-tocoferol, hierro, zinc y vitaminas H, B1, B2, B3, B5, B6 y B12 durante seis meses. Material y Método: estudio piloto unicéntrico, abierto, no aleatorizado, a simple ciego, de 180 días de duración, llevado a cabo en voluntarias con FAGA o ET. Se valoró el aspecto macroscópico del cabello, la densidad capilar mediante microfotografía, la relación anágena / telógena (A/T) mediante tricograma, el número de cabellos desprendidos mediante ensayos de peinado ("combing test") y de lavado ("wash test"). Se realizó una encuesta de autovaloración de los resultados. Resultados: la edad media de las participantes (n=10) fue de 40±15,5 años. El tiempo de evolución fue de 4,5±2 años y de tres meses para la FAGA y el ET, respectivamente. Al final del tratamiento las participantes presentaron un incremento medio del 6,9%, en la proporción de cabellos en fase anágena y la relación A/T media aumentó a 3,3. El 80% mostraron una mayor densidad capilar al finalizar el estudio. Al cabo de tres meses, todas las participantes presentaron una reducción media de la pérdida de cabellos del 56%, respecto de la visita basal. El 90% percibieron una mayor o igual cantidad de cabello al final del estudio y el 80% lo notaron más fuerte. No se registró ninguna molestia inducida por el tratamiento. Conclusiones: la buena evolución de las variables analizadas apunta a un beneficio terapéutico, frente a la FAGA y el ET. Estudios con mayor número de pacientes, son necesarios a futuro.(AU)

Introduction: female androgenetic alopecia (FAGA) and telogen effluvium (TE) are common causes of hair loss in women. A known fact in these types of alopecia is the increased activity of 5a-reductase which reduces testosterone to dihydrotestosterone, accelerating hair cycle and shortening its duration. Serenoa serrulata is a plant species whose components have an inhibitory effect on 5a reductase. Objective: the main objective of this study was to evaluate the efficacy and tolerance against female alopecia of a food supplement with Serenoa serrulata extract, L-cystine, tocotrienol-tocopherol complex, iron, zinc, and vitamins H, B1, B2, B3, B5, B6 and B12 administered daily for six months. Material and Methods: single-center, open-label, non-randomized, single-blind, 180-days pilot study conducted in women with FAGA or TE. The study assessed the macroscopic appearance of the hair, hair density by microphotograph, the anagen / telogen ratio (A/T) by trichogram, and the number of detached hair by combing and wash tests. Self-assessment survey of the results was performed. Results: the mean age of participants (n = 10) was 40 ± 15.5 years. FAGA and ET had an evolution of 4.5 ± two years and three months, respectively. After treatment the participants had an average increase of 6.9% in the proportion of hairs in anagen phase, and the mean A/T ratio increased to 3.3. Eighty percent or patients showed an increased capillary density at study end. After three months, all participants had a mean reduction of hair loss of 56% vs baseline. Ninety percent perceived a greater or equal amount of hair at the end of the study and 80% noticed it stronger. No adverse effects induced by treatment were observed. Conclusions: the good results of the analyzed variables suggest a therapeutic benefit against FAGA and ET. Additional research is warranted to confirm the observed data.(AU)

Androgenetic alopecia (male pattern hair loss) in the United States: what treatments should primary care providers recommend?

PURPOSE: Androgenetic alopecia (AGA), or male pattern hair loss, affects up to 96% of Caucasian men. Characterized by gradual thinning and eventual loss of hair along frontotemporal, parietal, and vertex areas of the scalp, AGA is associated with low self-esteem, depression, and dissatisfaction with body appearance. DATA SOURCES: In this systematic review of the literature, six primary research studies conducted in the United States are evaluated for their clinical application to primary care provider practice. CONCLUSIONS: Topical minoxidil 2%-5% 1 mL twice daily or finasteride 1 mg daily are recommended as first line treatments, followed by the use of Food and Drug Administration-cleared HairMax LaserComb® in patients who do not respond to first line modalities. IMPLICATIONS FOR PRACTICE: Further research in novel and established treatments is recommended, along with an evidence-based clinical practice guideline for practitioners in the United States.

Tratamiento farmacológico en la hiperplasia prostática benigna / Pharmacological treatment of the benign prostatic hyperplasia

La hiperplasia prostática benigna, enfermedad común en hombres a partir de los 50 años de edad, consiste en el crecimiento benigno e incontrolado de la glándula prostática y produce diversos síntomas del tracto bajo urinario. Su agente causal multifactorial involucra fundamentalmente el incremento de la conversión de testosterona en dihidrotestosterona por acción de la 5 a-reductasa prostática, lo cual desencadena eventos que propician el incremento en el tamaño de la próstata (componente estático) y el aumento del tono del músculo liso de vejiga y próstata (componente dinámico) regulado por los adrenoreceptores (ADR)-a1. El tratamiento farmacológico de la hiperplasia prostática benigna incluye los inhibidores de la 5a-reductasa, antagonistas de ADR-a1, su terapia combinada y la fitoterapia. El objetivo del presente trabajo fue presentar los aspectos más relevantes de la farmacología de los fármacos utilizados en el tratamiento de la hiperplasia prostática benigna y brindar elementos de su eficacia, seguridad y tolerabilidad. Para ello, se realizó una reseña de los diferentes fármacos utilizados en el tratamiento de esta afección, los que fueron clasificados de acuerdo con su mecanismo de acción. Se incluyeron productos de origen natural como los extractos lipídicos del Serenoa repens y Pygeum africanum, así como el D-004, extracto lipídico de los frutos de la Roystonea regia, que ejerce efectos beneficiosos sobre los principales factores causales de la hiperplasia prostática benigna, ya que es un inhibidor de la 5 a-reductasa prostática, un antagonista de los ADR-a1, un inhibidor de la 5-lipooxigenasa y tiene acción antioxidante, lo que evidencia un mecanismo multifactorial. Los resultados hasta el presente indican que el D-004 es seguro y bien tolerado(AU)

Benign prostatic hyperplasia is a common disease in over 50 years-old men consisting in uncontrolled and benign growth of prostatic gland that leads to lower urinary tract symptoms. The etiology of benign prostatic hyperplasia is multifactoral involving the increased conversion of testosterone in dihydrotestosterone by the prostatic 5a-reductase action, which brought about events that encourage the prostate growth (static component) and the increase of the bladder and prostate smooth muscle tone (dynamic component) regulated by the a1 -adrenoceptors (ADR). The pharmacological treatment of the benign prostatic hyperplasia includes the prostatic 5a-reductase inhibitors, the a1-adrenoreceptor blockers, their combined therapy and the phytotherapy. This paper was aimed at presenting the most relevant aspects of the pharmacology of drugs used for treating the benign prostatic hyperplasia, and providing elements to analyze their efficacy, safety and tolerability. To this end, a review was made of the different drugs for the treatment of this pathology and they were grouped according to their mechanism of action. Natural products were included as lipid extracts from Serenoa repens and Pygeum africanum as well as D-004, a lipid extract from Roystonea regia fruits, with proved beneficial effects on the main etiological factors of benign prostatic hyperplasia. D-004 is a prostatic 5a-reductase inhibitor, an a1-adrenoceptor antagonist, a 5-lipooxygenase inhibitor and has antioxidant action, all of which reveals a multifactoral mechanism. The results achieved till now indicate that D-004 is a safe and well-tolerated product(AU)

Tratamiento farmacológico en la hiperplasia prostática benigna / Pharmacological treatment of the benign prostatic hyperplasia

La hiperplasia prostática benigna, enfermedad común en hombres a partir de los 50 años de edad, consiste en el crecimiento benigno e incontrolado de la glándula prostática y produce diversos síntomas del tracto bajo urinario. Su agente causal multifactorial involucra fundamentalmente el incremento de la conversión de testosterona en dihidrotestosterona por acción de la 5 a-reductasa prostática, lo cual desencadena eventos que propician el incremento en el tamaño de la próstata (componente estático) y el aumento del tono del músculo liso de vejiga y próstata (componente dinámico) regulado por los adrenoreceptores (ADR)-a1. El tratamiento farmacológico de la hiperplasia prostática benigna incluye los inhibidores de la 5a-reductasa, antagonistas de ADR-a1, su terapia combinada y la fitoterapia. El objetivo del presente trabajo fue presentar los aspectos más relevantes de la farmacología de los fármacos utilizados en el tratamiento de la hiperplasia prostática benigna y brindar elementos de su eficacia, seguridad y tolerabilidad. Para ello, se realizó una reseña de los diferentes fármacos utilizados en el tratamiento de esta afección, los que fueron clasificados de acuerdo con su mecanismo de acción. Se incluyeron productos de origen natural como los extractos lipídicos del Serenoa repens y Pygeum africanum, así como el D-004, extracto lipídico de los frutos de la Roystonea regia, que ejerce efectos beneficiosos sobre los principales factores causales de la hiperplasia prostática benigna, ya que es un inhibidor de la 5 a-reductasa prostática, un antagonista de los ADR-a1, un inhibidor de la 5-lipooxigenasa y tiene acción antioxidante, lo que evidencia un mecanismo multifactorial. Los resultados hasta el presente indican que el D-004 es seguro y bien tolerado

Benign prostatic hyperplasia is a common disease in over 50 years-old men consisting in uncontrolled and benign growth of prostatic gland that leads to lower urinary tract symptoms. The etiology of benign prostatic hyperplasia is multifactoral involving the increased conversion of testosterone in dihydrotestosterone by the prostatic 5a-reductase action, which brought about events that encourage the prostate growth (static component) and the increase of the bladder and prostate smooth muscle tone (dynamic component) regulated by the a1 -adrenoceptors (ADR). The pharmacological treatment of the benign prostatic hyperplasia includes the prostatic 5a-reductase inhibitors, the a1-adrenoreceptor blockers, their combined therapy and the phytotherapy. This paper was aimed at presenting the most relevant aspects of the pharmacology of drugs used for treating the benign prostatic hyperplasia, and providing elements to analyze their efficacy, safety and tolerability. To this end, a review was made of the different drugs for the treatment of this pathology and they were grouped according to their mechanism of action. Natural products were included as lipid extracts from Serenoa repens and Pygeum africanum as well as D-004, a lipid extract from Roystonea regia fruits, with proved beneficial effects on the main etiological factors of benign prostatic hyperplasia. D-004 is a prostatic 5a-reductase inhibitor, an a1-adrenoceptor antagonist, a 5-lipooxygenase inhibitor and has antioxidant action, all of which reveals a multifactoral mechanism. The results achieved till now indicate that D-004 is a safe and well-tolerated product

Effect of antiandrogens upon the morphological development of gubernaculum and the testicular descent in rats / 대한비뇨기과학회지

We evaluated the effect of antiandrogens on both fetal and adult rats, noting especially the morphological changes in the gubernaculum and testicular descent. Two antiandrogens, flutamide and 5a-reductase inhibitor 4-methyl-4-aza-5-pregnane-3-one-20[s] carboxylate (4-MAPC) produce gross and histological changes in the gubernaculum, as well as having an effect on testicular descent. While the gubernacula of controls were like full water-drop at day 20 of gestation. the gubernacula of fetuses treated with flutamide were thin and elliptical and the gubernacula of fetuses treated with 4-MAPC were thin and elliptical or like small water-drop. The position of the gubernaculum was near the bladder neck and lower border of pelvic cavity, regardless of the antiandrogen treatment. But, the degree of invagination of gubernaculum into abdominal wall tended to be less in fetuses treated with either antiandrogen. The muscular layer of gubernaculum treated with either anti-androgen tended to be thinner than controls. In adult rats treated from embryo to adult with flutamide, atrophy of the sex accessory glands and hypospadias were occurred and the scrotums were bifid or undeveloped on one side which the testis remained in the abdomen. We feel that flutamide and 4-MAPC cannot interfere with trans-abdominal testicular descent, but can induce the morphological changes in gubernaculum with failure of the trans-inguinal testicular descent. Also, it would be suggested that the gubernaculum has not Wolffian duct like testosterone dependency shown in differentiation of epididymis, vas deferens and seminal vesicle, because of the presence of the effect of both flutamide and 4-MAPC on gubernaculum.