Abstract
In order to study male hypergonadotropic hypogonadism as completely as possible, and to evaluate its possible effects on muscle atrophy and sexuality, RIA or IRMA methods were used to measure the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, total (T) and free (FT) testosterone, estradiol (E), dihydrotestosterone (DHT), sex hormone binding globulin (SHBG), androstenedione (A) and 17-OH-progesterone (17-OH-P) in 29 patients with myotonic dystrophy (MD). The mean hormonal levels ±SD were: LH 8.0±4.4 mIU/ml, FSH 17.4±11.5 mIU/ml, A 200±130 ng/dl (all higher than in controls); T 406±290 ng/dl, FT 22.7±7.0 pg/ml, DHT 55.5±29.7 ng/ml (all lower than in controls). The low FT and DHT levels (never previously studied in MD) confirm the androgenic deficiency. The high androstenedione levels and low testosterone concentrations suggest defective enzyme 17-dehydrogenase. The duration of the disease correlated with both testosterone (r=−0.56) and FT levels (r=−0.59), showing that hypogonadism tends to worsen progressively. When the patients were divided into three groups on the basis of the severity of muscle involvement (A, B and C), LH and FSH levels were higher in group C (more severe disease) than in group A, respectively 9.3±4.7 and 20.6±12.3 mIU/ml versus 4.8±0.9 and 8.4±3.8, p<0.03; T levels were lower in group C than in group A, 337.3±263.4 ng/dl versus 649.7±320.3 (p<0.03); however, there was no significant difference in the FT levels of the three groups, which may imply that hypogonadism is unlikely to have a direct effect on muscle atrophy. About 25% of our patients were impotent; these subjects had higher LH and FSH (p<0.001) and lower FT levels than the patients who were not impotent (p<0.03). However, hypogonadism may not be the only cause of impotence as all of the impotent patients belonged to group C and had a very high (CTG)n triplet expansion. We hypothesise that hypogonadism and sexual impairment could be partially due to a muscle cell alteration: i.e. a dysfunction of both the testicular peritubular myoid cells and of the corpus cavernosum smooth muscle.
Sommario
Allo scopo di studiare in maniera completa l'ipogonadismo ipergonadotropo maschile nella distrofia miotonica e di valutarne le eventuali conseguenze sull'atrofia muscolare e sulla sessualità, sono stati determinati con metodo RIA o IRMA in 29 pazienti affetti da distrofia miotonica e in 34 soggetti sani: LH, FSH, prolattina, testosterone totale (T) e libero (FT), estradiolo (E), diidrotestosterone (DHT), SHBG, androstenedione (A), 17-OH-Progesterone. Le medie ± deviazione standard di questi ormoni sono risultati: LH=8.0±4.4 mIU/ml, FSH=17.4±11.5 mIU/ml, A=2.0±1.3 ng/ml, tutti più elevati dei controlli. T=406±290 ng/dl; FT=22.7±7.0 pg/ml, DHT 55.5±29.7 ng/dl tutti più bassi dei controlli.
Il riscontro di bassi valori di FT e DHT, non studiati prima d'ora in questi soggetti, conferma e rende più evidente il deficit androgenico. L'elevato livello di A con T basso dimostra un deficit dell'enzima 17-deidrogenasi. La durata della malattia correla significativamente sia con il tasso di T (r−0.56) che di FT (r−0.59) e quindi l'ipogonadismo tende ad aggravarsi progressivamente. Dividendo i nostri pazienti in tre gruppi (A, B, C) in base alla gravità del danno muscolare i livelli di LH e FSH erano più elevati (rispettivamente 9.3±4.7 and 20.6±12.3 mIU/ml vs 4.8±0.9 and 8.4±3.8, p<0.03) e T più basso (rispettivamente 337.3±263.4 ng/dl vs 649.7±320.3, p<0.03) nelle forme più gravi (gruppo A). Tuttavia tra i tre gruppi non sono state riscontrate variazioni del FT e quindi è poco probabile una influenza dell'ipogonadismo sulla atrofia muscolare. Circa il 25% dei pazienti lamentava impotenza sessuale. Questi soggetti avevano livelli di FSH e LH più elevati (p<0.001) e di testosterone libero più bassi (p<0.03) rispetto a chi aveva normale sessualità. Tuttavia l'ipogonadismo potrebbe non essere la sola causa dell'impotenza. Gli impotenti appartenevano tutti al gruppo C ed avevano una espansione della tripletta CTG molto alta.
È possibile che anche l'ipogonadismo e il deficit sessuale siano legati ad alterazioni di tessuto muscolare: le cellule miodi peritubulari del testicolo e la muscolatura liscia dei corpi cavernosi.
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The financial support of Theleton (Grant No. 640) is gratefully acknowledged.
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Mastrogiacomo, I., Bonanni, G., Menegazzo, E. et al. Clinical and hormonal aspects of male hypogonadism in myotonic dystrophy. Ital J Neuro Sci 17, 59–65 (1996). https://doi.org/10.1007/BF01995710
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DOI: https://doi.org/10.1007/BF01995710