due to partial maturation arrest responds to low dose estrogen-testosterone
combination therapy resulting in live-birth: a case report
Gynecologist, Arogya Niketan
Private Limited, Uttarpara 712 258- Kolkata, India
Androl 2002 Dec; 4: 307-308
infertility; maturation arrest; oligospermia; estrogen; testosterone
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 . 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 .
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
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.
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 . 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 ,
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,
Sah P. Role of low-dose estrogen-testosterone combination therapy in men
with oligospermia. Fertil Steril 1998; 70: 780-1.
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.
Tesarik J, Mendoza C, Greco E. In-vitro maturation of immature human male
germ cells. Mol Cell Endocrinol 2000; 166: 45-50.
Handelsman DJ, Wishart S, Conway AJ. Oestradiol enhances testosterone-induced
suppression of human spermatogenesis. Hum Reprod 2000; 15: 672-9.
to: Purushottam Sah, A2, Kishan Abason, Verma Road, Uttarpara-712258,
2002-06-24 Accepted 2002-08-08