FERTILITY AND STERILITY Vol. 27. No. 11.

November 1976
Copyright" 1976 The American Fertility Society Printed in U.SA.

INFERTILITY DUE TO HYPERPROLACTINEMIA AND ITS

TREATMENT WITH ERGOCRYPTINE

ELIAS S. CANALES, M.D., GERARDO FORSBACH, M.D., JORGE SORIA, M.D.,

AND ARTURO ZARATE, M.D.*

Department of Gynecologic Endocrinology, Hospital Gineco-Obstetricia No.1,

Instituto Mexicano del Seguro Social, Mexico D. F., Mexico

The precise and sensitive measurement be clomiphene nonresponders, since the

of blood prolactin (PRL) levels has been
of special interest in the diagnosis of
pituitary hypothalamic disorders. It has
been reported that some patients with
cromophobe pituitary adenomas or supra-
sellar tumors have hyperprolactinemia
without galactorrhea. 1 In this regard,
inflrtile amenorrheic women who do not
respond to clomiphene have been shown
to have elevated circulating prolactin
concentrations; the administration of
bromoergocryptine, which suppresses the
hyperprolactinemia, is followed by restor-
ation of ovulatory cycles in these
women. 2 These findings suggest that se-
rum PRL levels should be measured in
women with unexplained amenorrhea
and infertility; likewise, when it is not
possible to count on radioimmunoassay
methods to measure PRL in blood, treat-
ment with bromoergocryptine should be
attempted.
MATERIALS AND METHODS
Of 116 infertile women with secondary
amenorrhea of 6 months' to 2 years'
.. duration attending the outpatient steril-
ity service, 33 were found to have hyper-
prolactinemia. None of the 33 patients
had galactorrhea. Hirsutism or ovarian
enlargement was not present in these pa-
tients. All of the women were found to
Accepted June 9, 1976.
* Reprint requests: Dr. A. Zarate, Hospital Gineco-
Obstetricia No.1, G. Mancera 222, Mexico D. F.,
Mexico.
administration of 50 mg of clomiphene
for 5 days on at least three occasions
failed to elicit ovulation. Progestogen
withdrawal bleeding occurred in all pa-
tients. Detectable anatomical hypotha-
lamic-pituitary lesions were excluded by
x-rays of the sella turcica. Thyroid and
adrenal function was within normal
limits.
Serum PRL levels were measured by
radioimmunoassay. 3
RESULTS
The serum PRL levels of the 33 women
are shown in Figure 1. A comparison
with values found in patients with amen-
orrhea-galactorrhea is also shown. The
mean PRL level in this group was higher
(26 ng/ml) than the mean value observed
in normal women (10 ng/ml) , but lower
than that found in patients with amenor-
rhea-galactorrhea syndrome (90 ng/ml).
After 14 to 40 days of bromoergocryp-
tine therapy at a dosage of 1.25 mg twice
daily, 26 of the 33 women experienced
menstrual bleeding. Ovulation has been
documented in 20 women, and conception
has occurred in 7 patients. The obser-
vation period in this study has now been
4 months. No side effects have been re-
ported.
DISCUSSION
The demonstration of elevated PRL
levels in blood in association with second-

1335
1336 COMMUNICATIONS-IN-BRIEF November 1976

PRL at the ovarian level. These hypoth-

400 eses are supported by studies showing
200 --
h that suppression of elevated PRL levels
Ii- with bromoergocryptine in women with
140-
- amenorrhea-with or without galactor-
h PRL
120
100 ,.-
:--
rhea-results in resumption of cyclic
gonadotropin secretion, ovulation, and •
t-:-
ng/ml
80
- fertility. 5 On the basis of previous stud-
60
40
--- ..... ies 2 and the present one, it is sug-
...!L gested that infertile women with hyper-
20
0 ~ ."
NORMAL AN OVULATORY
At
-
IDIOPATHIC
prolactinemia with or without galactor-
rhea could benefit from the adminis-
WOMEN WOMEN AMENORRHEA
n=25 n=33 GALACTORRHEA
n=82
tration of a prolactin suppressor in order
FIG. 1. Basal serum PRL levels in normally
to achieve cyclic ovulation and preg-
menstruating women, infertile women without nancy.
galactorrhea, and women with idiopathic amenor-
rhea-galactorrhea. Mean PRL concentrations were
higher in infertile patients, but overlapped PRL Acknowledgment. Bromoergocryptine (CB-154)
concentrations in normally menstruating women. was supplied by Dr. J. Echegaray of Sandoz de
The patients with amenorrhea-galactorrhea had Mexico. •
the highest PRL levels.

ary amenorrhea and infertility without
galactorrhea underlines the importance of
these disorders. The diagnosis of pitui-
tary adenoma was discounted, since the
skull tomograms were normal; however,
the presence of pituitary tumors is
still a possibility since polytomography
of the sella was not done. In each case
a single measurement of the serum PRL
concentration was sufficient to demon-
strate hyperprolactinemia, since the PRL
levels were elevated in all patients of this
series.
The mechanism by which hyperpro-
lactinemia interferes with pituitary go-
nadotropin secretion and ovulation re-
mains to be elucidated. A different ef-
fect of high levels of PRL on the hypo-
thalamus and/or pituitary has been sug-
gested, 4 as well as a blocking effect of
REFERENCES
1. Zarate A, Canales ES, Villalobos H, Soria J,
Jacobs LS, Kastin AJ, Schally AV: Pituitary
hormonal reverse in patients presenting hyper-
prolactinemia, intrasellar masses, and amenor-
rhea without galactorrhea. J Clin Endocrinol
Metab 40:1034, 1975
2. Bohnet HG, Dahlen HG, Wuttke W, Schneider
HPG: Hyperprolactinemic anovulatory syn-
drome. J Clin Endocrinol Metab 42:132, 1976
3. Hwang P, Guyda H, Friesen H: A radioim-
munoassay for human prolactin: (affinity, chro-
matography/galactorrhea/amniotic fluid/men-
strual cycle/growth hormone). Proc Natl Acad
Sci USA 68:1902, 1971
4. Tyson JE, Khojandi M, Huth J, Smith B,
Thomas P: Inhibition of cyclic gonadotropin
secretion by endogenous human prolactin.
Am J Obstet Gynecol 121:375, 1975
5. del Pozo E, Varga L, Wyss H, Tolis G, Friesen
H, Wenner R, Vetter L, Uettwiler A: Clinical
and hormonal response to bromocriptin (CB-
154) in the galactorrhea syndromes. J Clin
Endocrinol Metab 39:18, 1974