Post by Max on Jun 13, 2005 18:27:41 GMT -5
Male libido
Decreased erections, decreased potence, possible erectile dysfunction
Hoffman la Roche itself has not seen a clear association between human exposure to (Ro)accutane and decreased potence [0]. In rats, androgens influenced the penile reflex arc, corpus cavernosum, and the perineal striated muscles. In reflex erection, erectile response to ES and penile NOS activity in the rat, T seems to be first converted to DHT, the more active androgen modality [1]. It is shown in various studies that the 5-alpha-r is inhibited in human subjects exposed to (Ro)accutane, and the inhibition was measured up to 50% in doses comparable to what is used in acne "therapy" [3]. The 5-alpha-r converts testosterone to the more potent androgen dihydrotestosterone. Nitric Oxide Synthase (NOS) has also found to be significantly impaired by supraphysiological doses of retinoic acid [4].
Under all penile conditions, systemic 5-HT levels were higher than those registered in the cavernous serum. Although 5-HT does not appear to be involved in postsynaptic transmission in the HCC, our results may provide evidence for a physiological significance of 5-HT in the control of penile flaccidity and detumescence [2]. Both systemic 5-HT levels and 5-HT receptor expression is suggested to be significantly lower in human subjects exposed to (Ro)accutane, due to inhibition of Sp1 and NF-Y phosphorylation, two transcription factors that are found to bind to the promoter regions of the TPH gene, and the 5-HT-receptors.
Sperm production, sperm count and sperm quality
Studies in the 1980s have frequently denied effects on spermatogenesis mediated by (Ro)accutane. One study found that "the percentage of morphologically normal spermatozoa was slightly reduced at the end of therapy; 12 weeks after completion of therapy it was significantly reduced (P less than 0.05)."
The authors conclude that "This could, however, be due to the short elimination half-life of 13-cis retinoic acid and have nothing to do with the drug. On impulse cytophotometry the spermatozoa DNS showed no significant changes. According to the results of the cytophotometric examination, contraceptive measures for men during treatment with 13-cis-retinoic-acid need not be made obligatory" [5].
Later research has found more clear links between retinoic acid and the spermatogenesis. Targeted mutagenesis of the retinoic acid receptor alpha (RAR alpha) gene has revealed its essential role in spermatogenesis. Although cells in all stages of spermatogenesis were detected in RAR alpha(-/-) testes, there was an increase in degenerating pachytene spermatocytes and a temporary developmental arrest in step 8-9 spermatids in the first wave of spermatogenesis, a delay in the onset of the second wave, and a temporary arrest in preleptotene to leptotene spermatocytes in the first, second, and third waves [6]. Also in other species a clear relation between retinoids and spermatogenesis has been found. The effect of retinoids on spermatogenesis in adult male gerbils (Gerbillus cheesemani) was studied using light and electron microscopy. Treatment with either 13-cis-retinoic acid or retinol acetate was given for 6 weeks and their effects were compared with controls. It was found that 13-cis-retinoic acid induced almost complete cessation of spermatogenesis and produced alterations in the cytoplasm of Leydig cells [7].
Decreased erections, decreased potence, possible erectile dysfunction
Hoffman la Roche itself has not seen a clear association between human exposure to (Ro)accutane and decreased potence [0]. In rats, androgens influenced the penile reflex arc, corpus cavernosum, and the perineal striated muscles. In reflex erection, erectile response to ES and penile NOS activity in the rat, T seems to be first converted to DHT, the more active androgen modality [1]. It is shown in various studies that the 5-alpha-r is inhibited in human subjects exposed to (Ro)accutane, and the inhibition was measured up to 50% in doses comparable to what is used in acne "therapy" [3]. The 5-alpha-r converts testosterone to the more potent androgen dihydrotestosterone. Nitric Oxide Synthase (NOS) has also found to be significantly impaired by supraphysiological doses of retinoic acid [4].
Under all penile conditions, systemic 5-HT levels were higher than those registered in the cavernous serum. Although 5-HT does not appear to be involved in postsynaptic transmission in the HCC, our results may provide evidence for a physiological significance of 5-HT in the control of penile flaccidity and detumescence [2]. Both systemic 5-HT levels and 5-HT receptor expression is suggested to be significantly lower in human subjects exposed to (Ro)accutane, due to inhibition of Sp1 and NF-Y phosphorylation, two transcription factors that are found to bind to the promoter regions of the TPH gene, and the 5-HT-receptors.
Sperm production, sperm count and sperm quality
Studies in the 1980s have frequently denied effects on spermatogenesis mediated by (Ro)accutane. One study found that "the percentage of morphologically normal spermatozoa was slightly reduced at the end of therapy; 12 weeks after completion of therapy it was significantly reduced (P less than 0.05)."
The authors conclude that "This could, however, be due to the short elimination half-life of 13-cis retinoic acid and have nothing to do with the drug. On impulse cytophotometry the spermatozoa DNS showed no significant changes. According to the results of the cytophotometric examination, contraceptive measures for men during treatment with 13-cis-retinoic-acid need not be made obligatory" [5].
Later research has found more clear links between retinoic acid and the spermatogenesis. Targeted mutagenesis of the retinoic acid receptor alpha (RAR alpha) gene has revealed its essential role in spermatogenesis. Although cells in all stages of spermatogenesis were detected in RAR alpha(-/-) testes, there was an increase in degenerating pachytene spermatocytes and a temporary developmental arrest in step 8-9 spermatids in the first wave of spermatogenesis, a delay in the onset of the second wave, and a temporary arrest in preleptotene to leptotene spermatocytes in the first, second, and third waves [6]. Also in other species a clear relation between retinoids and spermatogenesis has been found. The effect of retinoids on spermatogenesis in adult male gerbils (Gerbillus cheesemani) was studied using light and electron microscopy. Treatment with either 13-cis-retinoic acid or retinol acetate was given for 6 weeks and their effects were compared with controls. It was found that 13-cis-retinoic acid induced almost complete cessation of spermatogenesis and produced alterations in the cytoplasm of Leydig cells [7].