Vitamin A Therapy in Oligospermia

Transcription

1 Vitamin A Therapy in Oligospermia H. W. Horne, Jr., M.D.,* and Charlotte l. Maddock, M.D. OLGOSPERMA, a major cause of human infertility, has not yet been treated with success, in spite of the large number and variety of therapeutic agents used. t has been suggested by Eichenberger that vitamin A might be of some value. To test this hypothesis, high oral doses of an aqueous dispersion of vitamin A were given to 12 patients. METHOD Among the 12 patients with varying degrees of spermatogenic deficiency, the pretreatment sperm output of 7 was definitely within the range of infertility ( 7 to 68 million spermatozoa per ejaculate); of 3, it was borderline ( 98 to 202 million spermatozoa per ejaculate). The remaining 2 cases had only what has been termed "necrospermia" and "spermatozoa of low motility." All patients were treated orally with 100,000 units per day of an aqueous dispersion of vitamin At for a twelve-week period. From the eighth week on, 3 patients (Subgroup ) were given a supplemental dose of 100 mg. of vitamin E ( Eprolin-Lilly) daily; 5 patients (Subgroup ) received From the Sterility and Endocrine Clinic, Free Hospital for Women, Brookline, Massachusetts, and the Division of Nutritional Research, The Children's Hospital, Boston, Massachusetts, aided by funds from the Williams-Waterman Fund for the Combat of Dietarv Diseases and from The Nutrition Foundation, nc. " The authors wish to express their appreciation for the advice and suggestions generously offered by Dr. John Rock, Director of the Sterility and Endocrine Clinic, Free Hospital for Women; and Dr. S. Burt Wolbach and Dr. Paul Patterson of the Children's Hospital, Boston during this study, also to Miss Jean Nauss (of this clinic) for her considerable technical assistance. The author has deposited in the Library of the Harvard Medical School a copy of the full tabulation of the laboratory data upon which his conclusions are based. *Sidney Graves Memorial Fellow in Gynecology, Free Hospital for Women. f The vitamin A and a portion of the financial support of this study were supplied by Dr. Elmer Sevringhaus of the Hoffmann-La Roche Company. 245

2 246 HORNE & MADDOCK [Fertility & Sterility a second daily dose of 100,000 units of vitamin A; and the remaining 4 patients (Subgroup ) continued without supplementary vitamins. There were 3 patients without clinical evidence of hypothyroidisrp. who had been taking 0.13 Gm. of thyroid daily as treatment for oligospermia prior to the start of the study. This was continued throughout the twelve weeks. n addition to control determinations, fasting blood samples were drawn after one, two, four, eight, and twelve weeks of therapy for carotinoid and vitamin A determinations. Since vitamin A ingestion is said to affect cholesterol and lecithin levels,3 4 these determinations also were made on many of the above samples. Basal metabolism was determined at two, four, and twelve weeks on 7 patients as a supplementary metabolic check. Semen from each patient was studied, usually every two to four weeks during treatment and at least once between the sixteenth and twenty-second weeks (four to ten weeks after the end of therapy), except in 1 case where a specimen was unobtainable. All semen was collected after at least five days of abstinence from coitus. Sperm counts are reported as the total spermatozoa per ejaculate. RESULTS The values obtained in Case 10 have been deleted' from the analysis of the study for reasons to be discussed below. Determinations made on the remaining 11 cases reveal that carotinoid levels were not noticeably affected either in the total group or in the subgroups. Vitamin A determinations showed an average of about 30 per cent increase for the whole group during the first eight weeks of medication. The patients receiving vitamin E (Subgroup ) and those receiving double doses of vitamin A (Subgroup ) during the final four weeks, showed a further increase in the circulating vitamin A at twelve weeks. n contrast, Subgroup returned to below the pretreatment level at twelve weeks (Fig. 1). Cholesterol and lecithin values did not change appreciably, the average cholesterol being initially somewhat higher than is considered normal and the average lecithin being initially somewhat lower (Fig. 2). There was, though, at the twelfth week, a definite drop toward normal in the initially high cholesterol-lecithin ratio. 2 However, there are too few determinations to prove that these trends are characteristic. The meaning of these findings and whether or not they are true abnormalities are uncertain. There was no significant shift in the average basal metabolic rate through-

3 Vol.. 3, No. 3, 1952] VTAMN A 247 out the therapeutic course. Semen analyses varied for the individual cases, as is usual with oligospermic patients. However, the averages of the whole group remained remarkably stationary, and there was no definite trend _..,....,.J / /, p,..,.,....._ _ } &- - - Sub-Group ll Vitamin A U.S.P. units % <>---4 Sub-Groupm. Average Oarotinoids "(%... Average Total Sperm x106. Average B.M.R WEEKS FGURE 1. All patients were treated orally with 100,000 units per day of an aqueous dispersion of vitamin A for a twelve-week period. Subgroup consists of 3 patients who in addition received 100 mg. of vitamin E daily during the last four weeks of treatment. Subgroup consists of 5 patients who received a second daily dose of 100,000 units of vitamin A. Subgroup received no supplementary treatment. 20 found during administration of the supplemental medications. Of the patients considered, 1 (Patient 2) showed, unaccountably, an appreciable rise in sperm count in the follow-up period. This has persisted through the

4 248 HORNE & MADDOCK [Fertility & Sterility twenty-sixth week since the beginning of therapy. None of the other sperm counts varied from their usual range. Coincidentally, the wives of 3 of the 12 patients became pregnant during Average Lecithin Mg.%..... Average Cholesterol Mg.% - Average Cholesterol Lecithm 100 o.soo FGURE 2. 0~ ~------~--~~--~ ~ WEEKS Average values of lecithin and cholesterol during and after treatment of 11 patients with vitamin A. or directly after the therapeutic period. The wife of Patient 9 conceived between the fourth and eighth weeks of treatment. Pregnancy is thus far uncomplicated. The wives of Patients 1 and 2 became pregnant about the twentieth to twenty-fourth week after start of treatment. Both had spontaneous abmtions at about the tenth week of pregnancy in spite of supportive therapy. n these 3 cases, sterility with exposure had persisted for three, three, and five years respectively. On the other hand, all 3 wives had

5 Vol. 3, No. 3, 1952] VTAMN A 249 been pregnant at least once before, and each had aborted spontaneously at least once. t is thus possible that vitamin A therapy may have been helpful in ways not made evident by our analysis. Case 10 As mentioned above, the values obtained in Case 10 were deleted from this analysis because of the bizarre values obtained. This man was a chronic alcoholic of long standing, and has belonged to Alcoholics Anonymous for several years, both facts being discovered after therapy was started. t is felt that his vitamin A metabolism is grossly abnormal, and therefore his determinations are presented separately. Following the end of the therapeutic course, during which there was no real change in his sperm output, he was given relatively large doses of thyroid because of a persistently low BMR, subsequent to which his sperm output, interestingly, has increased markedly and has continued at a high level. CONCLUSONS The results offer no suggestion that in the normally nourished male vitamin A therapy in doses used will improve deficient spermatogenesis. Blood levels of vitamin A will rise on the average about 30 per cent, and if vitamin E or 100,000 units of vitamin A are supplemented to the basic 100,000 units per day, this rise may be accentuated. However, concurrent with the increased vitamin A blood level, no shift was noted in the indices of metabolism investigated. SUMMARY 1. Twelve men with defective spermatogenesis were given 100,000 units of an aqueous dispersion of vitamin A by mouth daily for twelve weeks, causing a rise of 30 per cent in the circulating vitamin A level. 2. Three of these patients (Subgroup ) received in supplement 100 mg. of vitamin E ( Eprolin-Lilly) for the final four weeks. 3. Five of these patients (Subgroup ) received in supplement a second daily dose of 100,000 units of vitamin A for the final four weeks. 4. The results in 1 case of a known chronic alcoholic were so bizarre as to be reported separately. 5. Subgroups and at twelve weeks showed some increase in average blood vitamin A level above their own eight weeks' average. 6. No change was noted in carotinoid, cholesterol, or lecithin blood levels, nor in basal metabolic rates during therapy. The initially high cholesterol/ lecithin ratio dropped toward normal during therapy.

6 250 HORNE & MADDOCK [Fertility & Sterility 7. Spermatogenesis was not affected by therapy. A single case showed an unaccountable marked improvement in sperm output after therapy was finished. 8. The wives of 3 patients, whose complaint had been secondary sterility, became pregnant either during therapy or directly after therapy was finished. Two of them had spontaneous abortions. These pregnancies do not seem referable to vitamin A therapy. REFERENCES 1. Eichenberger, Von E.: Gynaecologia Vol. 128, Fasc. 6:460, Gertler, M. M., and Garn, S.M.: Science 112:14, Lasch, F.: Klin. Wchnschr. 13:1534, Wendt, H.: Deutsche med. Wchnschr. 62:1213, Correction The annual banquet of the Society, previously scheduled for Sunday, June 8, will be held on Saturday, June 7, at 7 p.m. at the Standard Club, 320 Plymouth Court, Chicago, ll. The round table discussions originally scheduled for Saturday will be held on Sunday night, June 8, instead.