Long-Term Outcome of Male-Limited Gonadotropin-Independent Precocious Puberty

Abstract

Long-term outcome of five new cases of male-limited precocious puberty (MPP) is reported. Three patients had positive family history. One patient was untreated; 2 boys received cyproterone acetate (2.0-3.6 mg/kg/daily) without clinical effects. Two patients were treated with ketoconazole (600 mg/daily); in 1, GnRH analogue therapy (Buserelin, 1,600 µg/day) was added after 6 months of effective ketoconazole treatment for development of central precocious puberty. The other patient did not develop central puberty under ketoconazole treatment and improved his predicted adult height from 172.4 to 181.1 cm. Four patients reached final height [B.A. (therapy cyproterone acetate): age 22.0 years, -2.0 SDS; B.G. (untreated): age 15.5 years, -1.7 SDS; M.M. (therapy cyproterone acetate): age 19.5 years, -1.6 SDS; M.F. (therapy ketoconazole plus GnRH analogue): age 21.3 years, -2.2 SDS]; three had reduced testicular volume (B.A.: -1.6/-1.6 SDS; B.G: -2.1/-2.1 SDS; M.F.: -2.4/-1.9 SDS); one (M.F.) showed oligospermia. We concluded that in MPP cyproterone acetate treatment did not improve final height; ketoconazole was effective in reducing testosterone secretion, but its real effect on final height cannot be determined; the timing of central puberty may be precocious, suggesting that an adjunctive GnRH analogue treatment may be needed. In some patients, testicular impairment may be present in young adulthood.

Long‐term treatment of familial male‐limited precocious puberty (testotoxicosis) with cyproterone acetate or ketoconazole

“…described a boy with testotoxicosis successfully treated with cyproterone acetate. However, this treatment did not decrease pubertal and bone age progression in two other cases 6 . Testosterone aromatization to oestrogen was postulated as the potential cause of the poor result of this treatment, but the currently available data are not sufficient to evaluate the long‐term effects of cyproterone acetate on growth and sexual development of FMPP boys.…”

“…Another therapeutic approach for FMPP includes ketoconazole, a P450 cytochrome inhibitor that inhibits adrenal and testicular androgen biosynthesis 15 . The major side‐effect of ketoconazole, one of considerable concern, is hepatotoxicity 6,9,15,16 . A study of five patients with FMPP, three of them harbouring the same LHCGR mutation (M398T), showed that ketoconazole was well tolerated and effective in increasing adult height 9 .…”

Management and outcome of central precocious puberty

“…, 1986; Dacou‐Voutetakis & Karidis, 1993; Soliman et al. , 1997; Frenzel & Doerr, 1998) and familial or sporadic male‐limited precocious puberty (Bertelloni et al. , 1997; Holland et al.…”

Bicalutamide and Third-Generation Aromatase Inhibitors in Testotoxicosis

“…10 Despite oligospermia in some affected males, most men and women retain adequate fertility and, therefore, can pass along the mutation to subsequent generations. 5,11 …”