finasteride, Propecia
Usefulness of a 12-month treatment with finasteride in idiophathic and polycystic ovary syndrome-associated hirsutism.

Petrone A, Civitillo RM, Galante L, Giannotti F, D'Anto V, Rippa G, Tolino A.

Department of Obstetrics and Gynecology, School of Medicine, Federico II, University Naples, Italy.

OBJECTIVE: Hirsutism is considered as a skin disease due to increased 5 alpha-reductase activity in the pilosebaceous unit and finasteride is a drug that inhibits this enzymatic activity. This study showed the effectiveness of a chronic treatment with a selective 5 alpha-reductase inhibitor, finasteride, in idiopathic and PCOS-associated hirsutism. METHODS: Finasteride was administered orally at a daily dose of 5 mg for a period of 12 months to 20 women with IH and 20 women with PCOS. MAIN OUTCOME MEASURES: Each group was submitted to clinical (with Ferriman-Gallwey method) and serum hormonal (FSH, LH, 17 beta-estradiol, total and free T, delta 4-androstenedione, DHEAS; dihydrotestosterone, 3 alpha-androstanediol glucuronide) studies at baseline and after 3, 6 and 12 months of treatment. RESULTS: After 3 months of finasteride treatment, a significant decrease in the average hirsutism scores was recorded both in IH (p < 0.0001) and PCOS patients (p < 0.0001). A progressive significant decrease of hirsutism score was observed in IH patients after 6 and 12 months (p < 0.002) and in PCOS patients after 6 but not 12 months. In fact, the maximal therapeutic effect on the hirsutism was obtained after 12 months in the IH and 6 months in PCOS group.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10668160&dopt=Abstract finasteride Propecia



finasteride, Propecia
Measuring reversal of hair miniaturization in androgenetic alopecia by follicular counts in horizontal sections of serial scalp biopsies: results of finasteride 1 mg treatment of men and postmenopausal women.

Whiting DA, Waldstreicher J, Sanchez M, Kaufman KD.

Baylor Hair Research and Treatment Center, Baylor University Medical Center, Dallas, Texas 75246, USA.

Hair regrowth was evaluated by histologic analysis in men and women treated for androgenetic alopecia, by counting follicles in horizontal sections of scalp biopsies. Serial 4mm punch biopsies were taken at baseline and after 12mo of treatment from the transitional area of hair thinning between normal hair and vertex balding in men, and in an area of frontal/parietal thinning in women. Horizontal sections of reticular and papillary dermis were read by one observer, blinded to patient, treatment, and time. All terminal hair bulbs, terminal anagen and telogen hairs, and vellus and vellus-like miniaturized hairs were counted. Twenty-six men aged 18-41y, comprising 14 on finasteride 1 mg daily and 12 on placebo, and 94 postmenopausal women, aged 41-60y, comprising 44 on finasteride 1 mg daily and 50 on placebo, were evaluated. In the male study, the terminal hairs increased from a mean baseline count of 15.5-20.9 after 12mo of finasteride, versus 17.3-18.3 in the placebo patients. The miniaturized hairs decreased from 26.7 to 23.6 with finasteride versus 21.3-20.3 with placebo. The terminal-to-vellus ratio increased more in the finasteride than in the placebo patients, suggesting some reversal of the miniaturization process with finasteride. In the female study, no significant differences in follicular counts were found between the finasteride and placebo groups after 12mo of treatment. Follicular counts in horizontal sections provide an informative adjunct to noninvasive measures used in hair growth studies. Finasteride appears to be capable of reversing hair miniaturization in androgenetic alopecia in young to middle-aged men, but not in postmenopausal women.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10674382&dopt=Abstract finasteride Propecia



finasteride, Propecia
Neuroactive steroid 3alpha-hydroxy-5alpha-pregnan-20-one modulates electrophysiological and behavioral actions of ethanol.

VanDoren MJ, Matthews DB, Janis GC, Grobin AC, Devaud LL, Morrow AL.

Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7178, USA.

Neuroactive steroids are synthesized de novo in brain, yet their physiological significance remains elusive. We provide biochemical, electrophysiological, and behavioral evidence that several specific actions of alcohol (ethanol) are mediated by the neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP; allopregnanolone). Systemic alcohol administration elevates 3alpha, 5alpha-THP levels in the cerebral cortex to pharmacologically relevant concentrations. The elevation of 3alpha,5alpha-THP is dose- and time-dependent. Furthermore, there is a significant correlation between 3alpha,5alpha-THP levels in cerebral cortex and the hypnotic effect of ethanol. Blockade of de novo biosynthesis of 5alpha-reduced steroids using the 5alpha-reductase inhibitor finasteride prevents several effects of ethanol. Pretreatment with finasteride causes no changes in baseline bicuculline-induced seizure threshold but reverses the anticonvulsant effect of ethanol. Finasteride pretreatment also reverses ethanol inhibition of spontaneous neural activity in medial septal/diagonal band of Broca neurons while having no direct effect on spontaneous firing rates. Thus, elevation of 3alpha,5alpha-THP levels by acute ethanol administration represents a novel mechanism of ethanol action as well as an important modulatory role for neurosteroids in the CNS.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10684899&dopt=Abstract finasteride Propecia



finasteride, Propecia
The effect of minocycline on the metabolism of androgens by human oral periosteal fibroblasts and its inhibition by finasteride.

Soory M, Tilakaratne A.

Department of Periodontology, GKT Dental Institute, King's College, Caldecot Road, London, UK.

The antimicrobial minocycline has matrix-stimulatory effects on connective tissue and bone. The aim here was to study the effect of minocycline on 5alpha reduction of androgen substrates to 5alpha-dihydrotestosterone (DHT) in periosteal fibroblasts and the influence of the antiandrogen finasteride on this conversion. Confluent cultures of periosteal fibroblasts established from oral periosteum isolated from the bone surface were incubated in duplicate in multiwell dishes with two androgen substrates, [(14)C]-testosterone/[(14)C]-4-androstenedione, in the presence or absence of serial concentrations of minocycline or the antiandrogen finasteride or the two in combination for 24 h. The metabolites formed were solvent-extracted with ethyl acetate, separated by thin-layer chromatography and quantified using a radioisotope scanner. Both androgen substrates were metabolized to DHT and 4-androstenedione or testosterone. Minocycline stimulated the synthesis of DHT from these substrates by 75-83% at 20-30 microg/ml (n=4; p<0.01). Finasteride inhibited the 5alpha-reductase activity of these substrates by 3-5-fold at 1 microg/ml and 40-80% at 0.01 and 0.1 microg/ml (n=4; p<0.01), with little change in 17beta-hydroxysteroid dehydrogenase activity. Minocycline and finasteride in combination showed an intermediate response with one substrate. As finasteride inhibits the type 2, 5alpha-reductase isoenzyme associated with anabolic functions, these findings demonstrate target-tissue androgen metabolic activity in periosteal fibroblasts at baseline and in response to minocycline. This has implications for the reparatory potential of the diseased periodontium during adjunctive treatment with minocycline.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10708666&dopt=Abstract finasteride Propecia



finasteride, Propecia
The antigonadotropic action of testosterone but not 7alpha-methyl-19-nortestosterone is attenuated through the 5alpha-reductase pathway in the castrated male rat pituitary gland.

Bandivdekar AH, Karp R, Sundaram K, Kumar N.

Center for Biomedical Research, Population Council, New York, New York 10021, USA.

The enzyme 5alpha-reductase plays a significant role in the prostate to amplify the action of testosterone (T) by converting it to a more potent androgen, dihydrotestosterone (DHT). The role of 5alpha-reductase in the testosterone feedback inhibition of gonadotropin secretion from the pituitary has not been elucidated. Therefore, we investigated the role of 5alpha-reductase on T action in in vitro and in vivo models. Castration has been reported to increase the 5alpha-reductase activity in pituitary glands. Hence, the effect of castration duration on the conversion of T to DHT by pituitary homogenates and the responsiveness of pituitary monolayer cell cultures to gonadotropin-releasing hormone (GnRH) challenge exposure were investigated. Incubation of [3H]-T with pituitary homogenates showed that the conversion of T to 5alpha-reduced metabolites was two- to threefold greater in pituitaries from rats who had been castrated for 14 days compared with those castrated for 1 day. In addition, the GnRH-stimulated release of LH from monolayer cell cultures of pituitaries from rats castrated for 1 day was twofold greater, whereas that from rats castrated for 2 weeks was six- to sevenfold greater compared with basal luteinizing hormone (LH) release. Hence we used rats castrated for 2 weeks to elucidate the role of 5alpha-reductase in T feedback inhibition. The inhibitory effects of the androgens T, 19-nortestosterone (19-NT), and 7alpha-methyl-19-nortestosterone (MENT) at 3 different concentrations (10(-9), 10(-7), and 10(-5) mol/L) on GnRH-stimulated LH release from monolayer cell cultures of pituitaries from rats castrated for 2 weeks were examined. All 3 androgens showed dose-dependent inhibition of LH release. MENT showed the greatest inhibition, followed by 19-NT and T. In the presence of finasteride (a 5alpha-reductase inhibitor), the inhibition of LH released by T and 19-NT were significantly greater. The inhibitory effect of MENT, which does not undergo 5alpha-reduction, was not altered by finasteride. In an in vivo study, rats castrated for 2 weeks received T with or without finasteride. There was a significantly greater suppression of serum LH in rats receiving T plus finasteride compared with those receiving T alone. These results suggested that 5alpha-reductase in the pituitary is not obligatory for the inhibitory action of T on gonadotropin secretion in the castrated rat. The action of MENT, a nonreducible androgen, on the pituitary is not affected by 5alpha-reductase.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10714822&dopt=Abstract finasteride Propecia



finasteride, Propecia
Pharmacological effects of the lipidosterolic extract of Serenoa repens (Permixon) on rat prostate hyperplasia induced by hyperprolactinemia: comparison with finasteride.

Van Coppenolle F, Le Bourhis X, Carpentier F, Delaby G, Cousse H, Raynaud JP, Dupouy JP, Prevarskaya N.

Laboratoire de Physiologie Cellulaire, USTL, INSERM EPI 9938, Villeneuve d'Ascq, France. fvancopp pop.univ-lille1.fr

BACKGROUND: The growth of the prostate gland is mainly dependent on androgens. Other hormones, like prolactin (PRL), also influence prostate development. Our purpose was to analyze and compare the effects of two drugs (5alpha-reductase inhibitor) used in the therapy of benign prostatic hyperplasia: lipidosterolic extract of Serenoa repens (LSESR), and finasteride in an in vivo model of rat prostate hyperplasia induced by hyperprolactinemia. METHODS: Hyperprolactinemia was induced by 30 daily injections of sulpiride. Wistar rats received daily gavages of LSESR or finasteride. We used the following groups: control, castrated, castrated with a substitute testosterone (T), or 5alpha-dihydrotestosterone (DHT) implant. RESULTS: Hyperprolactinemia increases the wet weight and induces hyperplasia in the lateral prostate (LP). Unlike finasteride, LSESR significantly reduced LP growth and hyperplasia in castrated, DHT-implanted, and sulpiride-treated rats. CONCLUSIONS: Finasteride was only capable of inhibiting the effect of androgens on rat prostate enlargement. LSESR inhibited not only the androgenic but also the trophic effect of PRL in rat LP hyperplasia. Copyright 2000 Wiley-Liss, Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10725865&dopt=Abstract finasteride Propecia