NOTE. Restoration of Fertility with Gonadotropin and Bromocriptine in a Hypogonadal Man after Removal of Macroprolactinoma

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1 Endocrinol. Jpon. 1984, 31 (5), NOTE Restortion Fertility Gondotropin Bromocriptine in Hypogondl Mn fter Removl Mcroprolctinom REIKO DEMURA, EMI ODAGIRI, KAZUKO, JIBIKI, HIROSHI DEMURA, KAZUO SHIZUME, OSAMI KUBO* AND KOICHI KITAMURA* Dept. Internl Medicine Neurosurgery*, Tokyo Women's Medicl College, 10-Kwdcho, Ichigy, Shinjuku-ku, Tokyo 162 Abstrct A cse mle hypogondism fter removl mcroprolctinom ws successfully treted gondotropin. A 35-yer-old mn treted surgiclly for pituitry denom hd elevted plsm prolctin impired pituitry function fter the opertion. He ws on replcement hydrocortisone, levothyroxine testosterone depot long bromocriptine. Norml plsm testosterone levels chieved HCG, 3,000 IU three times week. The ddition 75 IU FSH dily restored spermtogenesis the sperm count reched the fertile rnge t the 11th month. Doses HCG FSH cut in hlf t the 10th month out ffecting the plsm testosterone levels. His wife ws impregnted t the 12th month gve birth to norml b girl. Though hyperprolctinemi, common cuse infertility in both sexes, is redily tretble, ssocited hypogondism due to impired pituitry function is serious problem. Combined HCG HMG therpy long bromocriptine successfully restored spermtogenesis in mn longsting postopertive hypopituitrism due to mcroprolctinom. Tble 1. Pituitry function tests.. Responses LH, FSH, TSH PRL to 100 pg LH-RH 500 b. Responses GH cortisol to 0.1 U/kg regulr insulin.. LH-RH, TRH test Cse Report M. K., 35-yer-old mn visited the hospitl 9 yers go for the evlution postopertive pituitry function s he underwent trnsfrontl hypophysectomy for pituitry denom which hd extended suprsel- b. ITT Received Mrch 5, 1984 * on replcement

2 652 DEMURA lry ws 169 cused cm feminine public sprce st. No reveled mrkedly levels (Tble t ly complete lter, he become Fig. 1. fther moderte low indicting but no on 7.5 mture Leydig In cells. plsm for 1100 strom, cells mle ng/dl smll the groups LH RIA NIAMDD, LH, germinl ng/ml, dispersion cell fibroblst-like FSH using own RIA kits rtibody kit kindly USA. Norml miu/ml, tubules edemtous our regulr testosterone testosterone using Mryl, FSH, Plsm 500 ƒêg (RIA) Jpn. prolctin ICL, 0.1 IU/kg Plsm tolernce LH-RH rdioimmunossy Seminiferous membrne Sertoli the mesured insulin 100,ƒÊg Eiken, ws rnges ( ~ 400). bsement composed immturity. Eight wnted biopsy performed simultneously, tests injecting supplied gondotropin testiculr Methods tests TRH respectively. mde mrked1). TRH mesured 125 mg/dy egerly then thickening minly exmintion (Fig. function insulin, t biopsy mrried Histology tubules zoospermi testes test levothyroxine depot strted Pituitry LH-RH prolctin Urologicl trophied yers mg/dy, Mterils tests therpy testosterone bromocriptine. reveled to 20 glc- hormones plsm strted. function ll ws hd testes Replcement or elevted weeks the Pituitry 1). 100 ƒêg/dy therpy He kg Axillry reserve hydrocortisone mg/2 58 gynecomsti noted. impired disturbnces. weighed structure. torrhe body hir smll visul tll Endocrinol. Jpon. October 1984 et l. 2-9 prolctin miu/ml, 275- respectively. generlly popultion trophic strom. The wsevidently cells detected

3 Vol. 31, No. 5 HCG, HMG THERAPY IN POSTOP. PROLACTINOMA 653 Fig. 2. Clinicl course before gondotropin tretment.

4 654 DEMURA et l. Endocrinol. Jpn. October 1984 Fig. 3. Clinicl course during gondotropin tretment.

5 Vol. 31, No. 5 HCG, HMG THERAPY IN POSTOP. PROLACTINOMA 655 Results The clinicl course before gondotropin tretment is shown in Fig. 2. Plsm prolctin remined low throughout this course. Plsm LH ws completely suppressed, but FSH levels in low norml rnge. Plsm testosterone levels in the low norml or subnorml rnge. The sperm count reveled complete zoospermi ll the time. The course gondotropin therpy is shown in Fig. 3. Plsm testosterone incresed to ner 500 ng/dl shortly fter injections HCG (HCG, Mochid phrm. Co.), 3,000 IU every second dy. To stimulte spermtogenesis, 75 IU FSH (Humegon, Snkyo Phrm. Co.) ws dded dily from the 3rd month. The combined HCG FSH therpy kept the plsm testosterone levels the sme s before norml libido, potence senstion well-being. At the 6 month therpy, 0.6 ~ 106/ml sperm ws counted for the first time. As plsm testosterone levels tended to be higher in the ltter 6 months tretment, doses HCG FSH reduced to hlf. Plsm LH FSH found to be , miu/ml throughout the course tretment except for interruptions for his own personl resons. Crossrectivities HCG, Mochid Humegon to LH ssy reveled to be % on unit bsis, while those Humegon HCG to FSH 7.5% for the former negligible for the ltter. Sperm counts grdully incresed reched fertile rnge 10.6 x 106/ml in the 11th month. His wife ws impregnted in the 12th month gve birth to norml b girl. Discussion Since the first report Gemzell Kjessler (1964) the successful tretment infertility in mn FSH, there hve been severl reports gndotropin therpy for mle hypogondotropic eunuchoidism (Johnsen, 1978 ; Luboshitzky et l., 1979 ; Mncini et l., 1979 ; Snten et l., 1973 ; Shill et l., 1979 Weinstein Reitz, 1974). Among these report concerning hypogondism due to hyperprolctinemi ws unusul (Luboshitzky, 1979). Although hyperprolctinemi is esily tretble, either mediclly or surgiclly, permnent hypogondotropic hypogondism ssocited prolctinom is very serious problem. The regimen gondotropin therpy hs been vried. We performed combined therpy HCG HMG for the restortion complete gondl function fertiltty. Plsm testosterone incresed immeditely to the norml rnge severl injections HCG lone, but spermtogenesis ws restored only fter the ddition 75 IU FSH dily for 6 months. There severl reports indicting tht HCG lone initited (Bremner et l., 1981) or mintined spermtogenesis fter it hd been initited combined therpy HCG HMG (Johnsen, 1978). It ws lso reported tht testosterone lone stimulted spermtogenesis in stlk-sectioned rhesus monkeys (Mrshll et l., 1983). In generl, reltively high doses HCG used in previous reports. Snten Pulsen (1973) used 4,000 IU HCG three times week in order to stimulte testosterone production. Weinstein Reitz (1974) dministered 5,000 IU HCG three times week to gondotropin deficient mle to chieve norml concentrtion plsm testosterone. Shill et l (1979) reported tht 2,000 IU HCG 75 IU FSH three times week resulted in successful spermtogenesis in 85% the eunuchoid ptients. It ws

6 656 DEMURA et l. Endocrinol. Jpon. October 1984 lso demonstrted in our present work tht firly lrge mounts HCG FSH required to mintin plm testosteone levels in the norml rnge. This my be due to refrctoriness the testes becuse long-sting secondry hypogondism. Plsm testosterone tended to be higher in lter period tretment, even to hlf the mount gondotropins, suggesting grdul recovery the responsiveness Leydig cells to gondotropin. On the other h, desensitiztion the testes during chronic tretment gondotropin ws pointed out D'Agt et l. (1982). Successful tretment hypogondl mn combintion gondotropin bromocriptine following n opertion for mcroprolctinom ws reported. Acknowledgements Authors deeply wish to thnk to Pr. N. Ssno, Dept. Pthology, Tohoku Univ. for exmining describing the findings testiculr biopsy. This work ws prtly supported reserch grnt for " Specific Diseses " from the Jpnese Ministry Helth Welfre, reserch grnt from the Jpnese Ministry Eduction. References Bremner, W. J., A. M. Mtsumoto, A. M. Sussmn C. A. Pulsen (1981). Follicle-stimulting hormone humn spermtogenesis. J. Clin. Inv. 68, D'Agt, D., E. Vicri, A. Aliffi, G. Mugeri, A. Mongiol S. Gulizi (1982). Testiculr responsiveness to chronic humn chorionic gondotropin dministrtion in hypogondotropic hypogondism. J. Clin. Endocr. 55, Gemzell, C. B. Kjessler (1964). Tretment infertility fter prtil hypophysectomy humn pituitry gondotrophins. Lncet 1, 644. Johnsen, S. G. (1978). Mintennce spermtogenesis induced HMG tretment mens continuous tretment in hypogondotropic men. Act Endocr. 89, Luboshitzky, R., E. Rosen, S. Trestin, I. M. Spitze. (1979). Hyperprolctinemi hypogondism in men. Clin. Endocr. 11, Mncini, R. E., A. C. Seigver, A. Perez Lioret (1969). Effect gondotropins on the recovery spermtogenesis in hypophysectomized ptients. J. Clin. Endocr. 29, Mrshll, G. R, E. J. Wickings, D. K. Ludecke E. Nieschlg (1983). Stimultion spermtogenesis in stlk-sectioned-rhesus monkeys testosterone lone. J. Clin. Endocr. 57, Snten, R. J. C. A. Pulsen. (1973). Hypogondotropic eunuchoidism. II. Gondl responsiveness to exogenous gondotropins. J. Clin. Endocr. 36, Shill, W. B. (1979). Recent progress in phrmcologicl-therpy mle subfertility. A review. Andrologi 11, Weinstein, R. L. R. E. Reitz (1974). Pituitrytesticulr responsiveness in mle hypogondotropic hypogondism. J. Clin. Inv. 53,

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