Oligospermia due to partial maturation arrest responds to low dose estrogen-testosterone combination therapy resulting in live-birth: a case report

Purushottam Sah

Asian J Androl 2002 Dec; 4: 307-308           

Keywords: infertility; maturation arrest; oligospermia; estrogen; testosterone

Abstract

A man having severe oligospermia, due to partial maturation arrest at spermatid stage, was given low dose estrogen-testosterone combination therapy for three months. His sperm count increased enormously, following which his wife conceived and delivered a healthy baby at term.

The author has reported earlier that low dose estrogen-testosterone combination therapy may increase the sperm count in some men with oligospermia [1]. Now, the case report of a man, who had severe oligospermia due to partial maturation arrest at spermatid stage, is being presented. Maturation arrest may occur at the primary spermatocyte, secondary spermatocyte or spermatid stage; in some cases arrest may be partial and few mature sperm may be produced, causing severe oligospermia [2].

Case report

A 34-year-old man, married for four years without having any child, attended the low-resource private clinic on August 28, 2000.

His semen analysis (SA), done on July 7, 1998, showed a sperm count (C) of 0.02510⁶  per mL, of which only few sperm were motile (M) and 15 % of them were of normal morphology (N). He received mesterolone 25 mg orally daily for three months and his SA, done on October 24, 1998, showed: C- 0.07510⁶ per mL, M- 40 % and N-15 %. Subsequently, he received clomiphene citrate 25 mg orally daily for few months. His SA was done on June 1, 2000 and again on August 1, 2000, and on both occasions it showed few weakly motile sperms only. The volume of the ejaculate was always normal (1.5 to 4.0 mL).

On August 11, 2000 testicular biopsy was done and it showed similar histological pattern in both the testes: number and diameter of seminiferous tubules were normal, majority of them showed maturation arrest at spermatid stage, while few tubules showed maturation up to spermatozoa stage; there was no thickening of tubular basement membrane and interstitium was normal.

His wife had regular menstruations; her tubal insufflation test showed patent tubes and endometrial biopsy showed it was in secretory phase. She had received clomiphene citrate. All these investigations and treatments were done before the infertile man attended the low resource private clinic.

The man did not have past history of any significant illness or sexual dysfunction, nor was he exposed to heat or chemicals. On physical examination: he was normotensive and androgenized; his testes were of normal consistency but the left one was a bit small in size, there was no evidence of any varicocele or any epididymitis.

Since no assurance of a cure could be given, the man refused to spend on costly hormonal assay and therapy. So, after taking informed consent, he was given low dose estrogen-testosterone combination therapy (ETCT). He received one tablet of combined low dose estrogen and testosterone orally daily (ethinyl estradiol 0.0044 mg and methyl testosterone 3.6 mg) for three months.

On November 6, 2000, seventy days after starting of the treatment, his SA showed: C- 3510⁶ per mL, M- 25 % and N-25 %. He took the ETCT for three months till November 28, 2000 and on December 12, 2000, his SA showed: C- 4010⁶ per mL, M- 28 % and N-32 %. His SA was repeated on February 9, 2001, seventy-three days after stopping of the treatment, and it showed: C- 2010⁶ per mL, M- 60 % and N-70 %. He did not report of any adverse effects and none were detected on physical examination.

His wife received clomiphene citrate 50 mg daily, from third to seventh day of her menstrual cycle, in January and February 2001; the dose of clomiphene was increased to 100 mg daily in March and no medicine was given in April 2001. She had her last menstruation on April 13, 2001 and on May 19, 2001 her urine examination showed positive pregnancy test. She attended government hospital for obstetrical care and delivered a healthy female child, weighing 3700 g, by Caesarean-section on January 17, 2002.

Discussion

Maturation arrest, at the primary spermatocyte stage and round spermatid stage, can be treated by in vitro culture and maturation followed by microm anipulation-assisted fertilization with elongated spermatid; birth of healthy babies has been reported [3]. This infertile man too could be treated with ICSI, which is very costly, while total cost of ETCT for three months was equivalent to six US dollars only.

This man had received mesterolone and clomiphene, but the sperm count remained less than 0.110⁶  per mL on four occasions between July 1998 and August 2000; his sperm count increased after taking ETCT and was more than 2010⁶  per mL on three occasions between November 2000 and February 2001.

Though combination of testosterone and estrogen, at higher doses, has been shown to have contraceptive effects in men [4], yet this case study is being reported so that it may stimulate interest in the conduct of further controlled studies; until then this low dose estrogen testosterone combination therapy, for the treatment of oligospermia, remains unproven.

References

[1] Sah P. Role of low-dose estrogen-testosterone combination therapy in men with oligospermia. Fertil Steril 1998; 70: 780-1.

[2] Sigman M, Howards SS. Male infertility. In: Walsh PC, Retik AB, Stamey TA, Vaughan Jr. ED, editors. Campbell's Urology. Philadelphia: W B Saunders' Co; 1992. p 675.

[3] Tesarik J, Mendoza C, Greco E. In-vitro maturation of immature human male germ cells. Mol Cell Endocrinol 2000; 166: 45-50.

[4] Handelsman DJ, Wishart S, Conway AJ. Oestradiol enhances testosterone-induced suppression of human spermatogenesis. Hum Reprod 2000; 15: 672-9.

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Correspondence to: Purushottam Sah, A2, Kishan Abason, Verma Road, Uttarpara-712258, Kolkata, India.

Tel: +91-33-663 8569

E-mail: purushottamsah@hotmail.com

Received 2002-06-24    Accepted 2002-08-08