Threatened Abortion and/or Progestins Therapy in Pregnancy as Cause of Precocious Puberty

Abstract

The inhibition of gonadotropin secrction in childrcn with central precocious puberty trcatcd with LII-RH analogues rcsults in suppression of the pubertal development, including growth vclocity. In some paticnts, a marked slowing of growth is observed. To test whcther this is rclatcd to inhibi ion of GH sccretion, we performed a clonidine test (150 mcg/m5 p.0.) in 9 girls with central prccocious puberty (age range: 4 4/12 to 11 8/12 yrs) treated with D-TRP-6-LH-RH, a supcractivc LH-RII analogue, 6 by daily s.c. injections of an acqucous prcparation, and 3 by monthly i.m. injections of a depot preparation (DecapcptylFerring). The daily dose ranged from 1.5 to 3 mcglkglday and thc trcatmcnt periods were from 10 to 60 months. In all paticnts a normal GH response was found, by a peak valuc of 18 ng/ml or higher. In all, gonadotropin suppression was confirmed by a concomitant i.v. LH-RH test. These data show that GI1 reserve is not affcctcd by the LH-RH analogue therapy and cannot be implicated in the slowing of growth, which is probably duc to lack of sex hormones. P e r i o d i c i n t r a m u s c u l a r i n j e c t i o n o f LRH-M has been shown t o suppress p i t u i t a r y -g o n a d a l a x i s i n c h i l d r e n w i t h precocious p u b e r t y (Roger e t a l . ESPE 1984). I n o r d e r t o assess t h e e f f e c t s o f LRH-M on spermatogenesis, 50 vg/kg were g i v e n t o Fox dogs on days 1 and 21, then e v e r y 28 days. I n t h e a d u l t dogs t r e a t e d f o r 15 weeks spermatogenesis was i n h i b i t e d d u r i n g t h e r a p y and recover e d 90 days a f t e r t h e l a s t i n j e c t i o n . A one-year treatment was s t a r t e d i n 3 adolescent dogs j u s t b e f o r e completion o f puberty.LH l e v e l (ng/ml , Risem) decreased f r o m 4.6 ' 0.6 t o 1.2 + 0.1 on day 21 (p<0.05) and became u n d e t e c t a b l e beyond t h e 5 t h i n j e c t i o n . Normal o r h i g h l e v e l s were recovered 60 days a f t e r t h e l a s t i n j e c t i o n . Mean t e s t o s t e r o n e l e v e l (ng/ml) was 1.6 20.2 i n i t i a ll y , u n d e t e c t a b l e beyond t h e 5 t h i n j e c t i o n and 1 . 3 2 0 . 3 s i x t y days a f t e r t h e l a s t i n j e c t i o n . H i s t o l o g y o f t h e r i g h t t e s t i s on day 371 showed spermatogonia i n a l l tubes, spermatocytes I i n 5 t o 57% o f tubes and absence o f more mature c e l l s . I n i t i a l l y , no spermatozoa were p r e s e n t i n e j a c u l a t e s , b u t i n 2 dogs sperm c e l l s were p r e s e n t f r o m days 56 t o 77 and 64 t o 105 r e s p e c t i v e l y , d i s a p peared t h e r e a f t e r and reappared 92 days a f t e r t h e l a s t i n j e c t i o n . No sperm c e l l s were found i n t h e 3 r d dog throughout t h e study. T h i s work shows t h a t LRH-M induces a r e g r e s s i o n o f spermatogenes i s i n adolescent dogs and t h a t recovery occurs a f t e r treatment. 128 12 hrs urine collections were made in patients presenting with central PP receiving the GnRH agonist B, either subcutaneously (SC) (13 g...