Low-Dose Cortisone for Male Infertility

Vol. 29, No.2, February 1978

FERTILITY AND STERILITY

Printed in U.s.A.

Copyright' 1978 The American Fertility Society

LOW-DOSE CORTISONE FOR MALE INFERTILITY

DAVID T. UEHLING, M.D.*

Division of Urology, University of Wisconsin Center for the Health Sciences, Madison, Wisconsin 53706

Thirty-eight males with idiopathic infertility were randomly treated with low-dose thyroid and low-dose cortisone. Pregnancy followed treatment with cortisone in 7 of 33 courses and followed treatment with thyroid in 4 of 30 courses (P = 0.5, not significant (NSl.!. The mean pretreatment count in all patients was 12.3 million/ml. The mean post-treatment count with thyroid was 11.2 million/ml as compared with 13 million/ml for cortisone treatment (P = 0.4, NS). Pretreatment motility was 45% as compared with 44% following thyroid treatment and 43% following cortisone treatment (P = 0.7, NS). The pregnancy rate seemed to correlate with pretreatment counts rather than with the type of treatment. The efficacy of low-dose cortisone for idiopathic fertility would seem to be in question.

Many men with infertility do not have a specific identifiable etiology for their oligospermia. For such idiopathic infertility, one currently popular treatment is low-dose cortisone. 1 , 2 The pregnancy rates following low-dose cortisone in comparison with those obtained after other empiric treatments are difficult to discern from the available literature. In this study the effectiveness of low-dose cortisone treatment is compared with that of another type of empiric therapy, low-dose thyroid, in the treatment of idiopathic male infertility. METHODS

Thirty-eight men were seen from 1970 to 1975 with the primary complaint that their wives had not conceived. The wives also had been evaluated and none was judged to have an irremediable reason for failure to conceive. Semen analysis was carried out by a standard method on freshly ejaculated specimens. 3 The diagnosis of male infertility was based on the history of no pregnancies after 2 years of unprotected intercourse, a negative evaluation of the wife, Received September 6,1977; accepted September 22,1977. *Reprint requests: David T. Uehling, M.D., Division of Urology, University of Wisconsin Hospitals, 1300 University Avenue, Madison, Wisc. 53706.

and a sperm count of less than 40 million/ml. At least three sperm counts for each male were . performed prior to treatment and three counts during each type of treatment. The infertility was judged to be idiopathic after a negative evaluation including history, physical examination, sperm counts, urine analysis, complete blood count, and determination of serum or urine levels of gonadotropins and testosterone, proteinbound iodine or T3-T4' and urinary 17-ketosteroids and 17-hydroxysteroids. Testicular biopsy was performed too infrequently to correlate treatment results with biopsy findings. Drug treatment for the patients was prospectively randomized between cortisone acetate, 2.5 mg four times daily, and U.S.P. thyroid, 1 grain daily. Patients whose wives did not conceive during the first regimen then received the other medication. Since pregnancies occurred in only 11 wives, most patients received both types of treatment. Mean pretreatment counts and motility were compared by Student's t-test with counts and motility during treatment. The first count during each treatment was obtained at least 2 months after the treatment was initiated. Ten patients received 6 months of therapy with 5 mg of cortisone acetate after failing to impregnate their wives while taking the lower cortisone dose o~ thyroid. 220

COMMUNICATIONS-IN-BRIEF

Vol. 29, No.2

TABLE 1. Results of Treatment with Low-Dose Cortisone or Thyroid"

221

Sperm counts ranged from 1 to 40 million/ml and motility from 10% to 90% before and during treatment. Pregnancy followed treatment with thyroid in 4 of 30 courses and with cortisone in 7 of 33 courses

0.05) than 27 patients whose wives did not become pregnant. No pregnancies occurred among the wives of the 10 patients receiving 5 mg of cortisone acetate, nor were mean counts or motility changed.

Low-dose cortisone for idiopathic infertility has more recent advocacy. I, 2 However, in this study it did not improve mean sperm counts or motility. In addition, it did not result in more pregnancies than did thyroid. Stewart and Montie2 reported 6 pregnancies among 43 patients treated (11 were lost to follow-up) with the same cortisone acetate dosage. This represents a 14% pregnancy rate, which is similar to the rate reported here and to that achieved with placebo therapy. An alternative dosage of 5 mg four times daily has also been recommended, I but no pregnancies occurred during its usage in this study. At the current time, it is difficult to select empiric treatment for idiopathic infertility. Although clomiphene citrate appears to be another possibly useful agent,4 the question of whether mean sperm counts are significantly improved remains to be answered. As new types of therapy are tried, it may not be possible to compare them with placebo therapy. However, therapy should at least increase mean sperm counts. Progress in treatment modalities for male infertility more likely will result from narrowing the idiopathic group by delineation of other specific endocrine abnormalities such as the recently described hyperprolactinemiarelated infertility.5 By such delineations, more patients might be removed from the idiopathic, and largely untreatable, categories of male infertility.

DISCUSSION

REFERENCES

Mean count (million/m!) Mean motility (%)

Pretreatment

After cortisone treatment

After thyroid treatment

12 ± 8

13 ± 7

11 ± 9

45 ± 2

43 ± 2

44 ± 2

"Values are means ± standard deviation. RESULTS

Low-dose thyroid and its derivatives have a long history of usage in unexplained male infertility despite lack of documentation of efficacy or therapeutic rationale. Whether thyroid, 1 grain daily, can be considered to be a placebo is open to question. In the current climate of opinion on research with human subjects, thyroid is as close to a placebo as seems reasonable, and the 13% pregnancy rate during thyroid treatment might be considered approximately what might have occurred during observation alone.

1. Jefferies WM, Weir WC, Wein DR, Prouty RC: The use

2. 3. 4. 5.

of cortisone and related steroids in infertility. Fertil Steril 9:145, 1958 Stewart BH, Montie JE: Male infertility: an optimistic report. J Urol 110:216, 1973 Amelar RD, Dubin L, Walsh PC: Male Infertility. Philadelphia, WB Saunders Co, 1977 Paulson DF, Wacksman J: Clomiphene citrate in the management of male infertility. J Urol 115:73, 1976 Segal S, Polishuk WZ, Ben-David M: Hyperprolactinemic male infertility. Fertil Steril 27:1425, 1976