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SUMMARY

Studv Title and Investiqators

A Mu1 ticentre Study of D-Trp'-LHRH Mi crospheres (Decapeptyl Control 1 ed Re1 ease) in the Treatment of True Precocious Puberty. The study code is 45C02/AD/P01.

Investigators were:

Dr S.L.S. Drop (coordinator), Dept. Endocrinology, Sophia's Children Hospital, Rotterdam Dr R.J.H. Odink (coordinator) , Dept Paediatrics, Free University Hospital, Amsterdam Dr W. Oostdi jk, Dept Paediatrics, University Hospital, Leiden Dr B.J. Otten, Dept Paediatrics, University Hospital St-Radboud, Ni jmegen Dr M. Jansen, Wil helmina's Children Hospital , Utrecht Dr J.J.J. Wael kens, Dept Paediatrics, Catharina Hospital , Eindhoven Dr C.W. R O U W ~ , Dept Paediatrics, University Hospital, Groningen Dr M.H. Gons, Dept Paediatrics, Municipal University Hospital , Amst erdam

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S ummar Y

The objective of this study is to evaluate the effectiveness, safety and to1 erabi 1 i ty of sl ow re1 ease D-Trp'-LHRH mi crospheres in the treatment of central precocious puberty. The effectiveness is determined by the ability to fulfil the following therapeutic goals:

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1. t o suppress the secretion of gonadotropins and par t icular ly of gonadal s teroids down t o prepubertal level S;

2. t o slow down, ha l t or reverse the development o f secondary sex charac te r i s t ics , including s t o p of menstruation i n g i r l s ;

3. t o i n h i b i t the rapidly advancing skeletal maturation and t o normalize the accelerated growth velocity, thus

4. t o improve predicted adult height

T h i s multicentre study was open and non-comparative. 39 pat ien ts entered the study. 37 completed the 2 years of study and are reported here. O f these pat ients , 25 had n o t been treated before (group l ) , whereas 12 had been treated w i t h e i ther buserelin or cyproterone acetate (group 2 ) . Except for two g i r l s , the patients received one syringe of Decapeptyl CR containing 3.75 mg t r i p to re l in every 4 weeks.

Basal p l asma 1 utei n i zi ng hormone (LH) and basal p l asma fol 1 i cl e st imulating hormone (FSH) levels decreased significantly i n group 1. P1 asma oestradiol 1 evel S in the g i r l S decreased t o prepubertal 1 evel S i n both groups. In almost a l l patients the cl inical signs of precocious gonadarche such as breast development and menstruations ( g i r l s ) and an increased t e s t i s volume (boys), did not fur ther progress and even regressed i n several patients. 1 Growth velocity decreased i n the g i r l s o f group 1 from 10.4 cm/year (mean) i n the l a s t half-year before treatment t o 6.9 i n the f irst half-year of treatment and t o 4.7 cm/year i n the f o u r t h , t ha t is, the l a s t half-year. The ABAIACA r a t i o decreased during treatment i n the children, resulting i n an improvement of adult height prediction of 1.0 cm (mean) a f t e r one year of Decapeptyl CR. After two years, mean predicted adult height had increased 3.4 cm.

October 9, 1992

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After the f i r s t 4 weeks of therapy, 10% o the girls reported vaginal bleedings u p t o three times. Only one serious adverse event i s reported, fatigue and collapses. I t i s very unlikely t h a t Decapeptyl C R contributed t o this.

I t i s concluded t h a t Decapeptyl CR is clearly more e f fec t ive and safer than cyproterone acetate. Furthermore the efficacy r e su l t s are among the be t te r 2 year resul ts reported against central precocious puberty.

October 9, 1992