FERTILITY AND STERILITY Vol. 54, No.

5, November 1990
Copyright~ 1990 The American Fertility Society Printed on acid-free paper in U.S.A.

Hormonal treatment of functional ovarian cysts:

a randomized, prospective study*

Michael P. Steinkampf, M.D.t

Karen R Hammond, M.S.N.
Richard E. Blackwell, Ph.D., M.D.

Department of Obstetrics and Gynecology, Division of Reproductive Biology and Endocrinology,

The University of Alabama at Birmingham, Birmingham, Alabama

Estrogen (E)/progestin therapy for functional ovarian cysts is widely used in clinical practice,
but the efficacy of this treatment has not been determined in controlled trials. In this study, we
examined the effect of E/progestin administration in a group of infertility patients enrolled in a
program of ovulation induction who had cysts identified by transvaginal sonography. Patients
were randomized to receive either norethindrone 1 mg/mestranol 0.05 mg/d (group A, n = 24) or
no treatment (group B, n = 24) for up to 6 weeks. Patients were re-evaluated by sonography at 3,
6, and 9 weeks after entry into the protocol. The ages, mean cyst diameters, and proportions of
patients having received gonadotropins in the previous menstrual cycle were not significantly
different among the two groups. All patients who had a sonographic abnormality persisting for 9
weeks were surgically explored and found to have pathological cysts. The rate of disappearance of
functional ovarian cysts was not affected byE/progestin treatment. Fertil Steril54:775, 1990

The management of the cystic adnexal mass in
women of reproductive age remains a common gy-
necological problem. It is widely accepted that
many adnexal cysts represent a persistence of an
ovarian follicle or cystic corpus luteum. 1 Adminis-
tration of an oral contraceptive has been advocated
when a cystic mass is identified to hasten the reso-
lution of these "functional" ovarian cysts, 2 pre-
sumably by suppression of pituitary gonadotropin
release or a direct effect on the gonads. In a series
of 286 patients with a cystic adnexal mass who were
treated with a variety of E/progestin combinations
for 6 weeks, Spanos3 found complete resolution of
functional cysts. Although this treatment seems to
have become an accepted clinical practice, con-
trolled trials to document the efficacy of this ap-
proach are lacking. Because women frequently de-
velop functional ovarian cysts after ovulation in-
duction,4·5 this population provides a convenient
model for the investigation of this disorder. The
purpose of the present study was to determine
whether administration of a commonly used E/
progestin preparation hastens the resolution of ad-
nexal cysts identified in infertility patients en-
rolled in a program of ovulation induction.

Received May 30, 1990; revised and accepted July 18, 1990.
* Presented in part at the 37th Annual Meeting of The Amer-
ican College of Obstetricians and Gynecologists, Atlanta, Geor-
gia, May 20 to 25, 1989.
t Reprint requests: Michael P. Steinkampf, M.D., Depart-
ment of Obstetrics and Gynecology, University of Alabama at
Birmingham, University Station, Birmingham, Alabama
3,5294.
MATERIALS AND METHODS
This research protocol was reviewed and ap-
proved by the Institutional Review Board for Hu-
man Use of the University Alabama at Birming-
ham. Patients planning to undergo a cycle of
ovulation induction with clomiphene citrate (Sero-

Vol. 54, No.5, November 1990 Steinkamp! et al. Therapy of functional ovarian cysts 775
phene; Serono Laboratories, Norwell, MA) and/or
human menopausal gonadotropin (Pergonal or
Metrodin; Serono Laboratories), who were found
to have an adnexal cyst with a mean diameter ~ 1.5
em as identified by transvaginal sonography were
considered for this study. After consent was ob-
tained, patients were randomized to receive a com-
bination of norethindrone 1 mg and mestranol 50
Jlg/d (Ortho Novum 1/50; Ortho Pharmaceuticals,
Raritan, NJ) for up to 6 weeks (group A), or to ex-
pectant management (group B). Sonography was
repeated at 3, 6, and 9 weeks after entry into the
study. Ifpersistence of the cyst was observed for 9
weeks, the patient was referred for surgical evalua-
tion.
Patient characteristics were analyzed using a
two-tailed t-test or Fisher's two-tailed exact test,
as appropriate. Fisher's one-tailed exact test was
employed for comparisons of patient group out-
comes. Differences associated with a P value of
~0.05 were considered statistically significant.
Analyses were performed using the SAS-PC statis-
tical analysis package (Release 6.03; SAS Institute
Inc., Cary, NC).
RESULTS
Twenty-four patients were entered into each
treatment group. There was no significant differ-
ence in mean patient age (group A: 32.8 years,
group B: 31.5 years, P = 0.24) or the mean diameter
of the largest cyst (group A: 3.0 em, group B: 2.9
em, P = 0.92). The number of patients in each
group who had received gonadotropins in the previ-
ous cycle were similar (group A: 20 of 24, group B:
17 of 24, P = 0.49). One patient did not comply with
the study protocol and was excluded from the anal-
ysis. In 6 patients, a sonographic abnormality per-
sisted for 9 weeks. All6 patients were surgically ex-
plored and found to have pathological cysts (endo-
metriomas in 3, hydrosalpinges in 3). Of the
remaining women, the adnexal cysts had resolved
within 3 weeks in 20 (91%) of 22 patients in group
A, and in 16 (84%) of 19 patients in group B
(P = 0.428). At 6 weeks, the cysts had resolved in
all but 1 patient each in groups A and B (95.5% and
94.7%, respectively, P = 0.718). By 9 weeks, the
cysts had resolved in all the remaining patients
(Fig. p.
776 Steinkamp{ et al. Therapy of functional ovarian cysts
Patients without cysts (%)
100
80
60
--
40
Group A
20
Group B
3 6 9
Weeks
Figure 1 Cumulative percentages for the disappearance of
functional ovarian cysts. Group A: E/progestin; group B: expec-
tant management. *, P = 0.428; **, P = 0. 718.
DISCUSSION
To our knowledge, this is the first randomized,
prospective, controlled study of the effect of hor-
monal therapy on adnexal cysts in women of repro-
ductive age. We were unable to demonstrate a sig-
nificant effect of E/progestin treatment on the dis-
appearance of functional ovarian cysts over that
seen with expectant management. Because in the
present study the majority of patients with func-
tional cysts had undergone ovulation induction in
the cycle before study enrollment, our findings can
be generalized only with caution to spontaneously
ovulating women. However, the results of this
study point out the need for further research re-
garding the pathophysiology of functional ovarian
cysts, which represent a significant health problem
among reproductive-age women. 6 Although it is
generally accepted that E/progestin treatment pre-
vents the formation of functional ovarian cysts, 7
there remains little evidence that these medica-
tions are effective in hastening the disappearance
of these cysts once they are formed. Although the
morbidity involved with a brief trial of hormonal
therapy is generally considered to be low, patients
who receive this treatment and subsequently un-
dergo exploratory surgery for a persistent adnexal
cyst may be at increased risk for postoperative
thromboembolism. 8 •9 In conclusion, the findings of
our study indicate that E/progestin therapy is not
effective for the treatment of functional ovarian
cysts, at least among women who have recently un-
dergone ovulation induction.
Fertility and Sterility
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Steinkamp£ et al. Therapy of functional ovarian cysts 777