Clinical Endocrinology (2004) 60, 120–124 doi: 10.1046/j.1365-2265.2003.01948.x
120 © 2004 Blackwell Publishing Ltd
Blackwell Publishing, Ltd.
FSH and LH responses to GnRH after ovariectomy in
postmenopausal women
K. C. Dafopoulos*†, C. P. Kotsovassilis‡,
S. D. Milingos*, A. T. Kallitsaris*, G. S. Georgadakis†,
P. G. Sotiros‡ and I. E. Messinis*
* Department of Obstetrics and Gynaecology, University of
Thessalia, Larissa, † State Department of Obstetrics and
Gynaecology, General Hospital of Volos, Volos, and ‡ State
Department of Clinical Chemistry, General Hospital of
Athens, Athens, Greece
(Received 3 February 2003; returned for revision 24 February
2003; finally revised 13 May 2003; accepted 6 October 2003)
Summary
OBJECTIVE Whether the postmenopausal ovary is still
playing a role in the control of gonadotrophin secretion
in response to GnRH has not been investigated. The
aim of the present study was to test this hypothesis
by examining changes in basal and GnRH-induced
gonadotrophin secretion in postmenopausal women
after bilateral ovariectomy.
DESIGN The responses of LH and FSH to GnRH [10 μg
intravenously (i.v.)] were investigated in postmenopau-
sal women from 2 days before to 8 days after total
abdominal hysterectomy plus bilateral ovariectomy.
PATIENTS Nine postmenopausal women aged 52–
67 years and between 5 and 15 years after menopause.
In all cases the ovaries were histologically normal.
MEASUREMENTS Pituitary responses to GnRH were
calculated every 12–24 h as the net increases in LH
(∆LH) and FSH (∆FSH) at 30 min above the basal val-
ues. Basal values of oestradiol (E2) and testosterone
were also measured.
RESULTS Basal values of FSH showed a significant
decrease on postoperative days 2 ( P < 0·01) and 8
( P = 0·03) as compared to day 0, while at the same time
points after the operation LH values were marginally
lower than on day 2 ( P = 0·05). Serum E2 values showed
a gradual increase up to postoperative day 1 ( P = 0·04)
and a gradual decline thereafter. Basal testosterone
concentrations decreased gradually and significantly
after ovariectomy and were significantly lower on day
8 than on day 0 ( P < 0·01). ∆ FSH and ∆ LH responses to
GnRH did not change significantly with time. A temporary
increase at 12 h after the operation was not significant.
CONCLUSIONS These results demonstrate for the first
time that the removal of the ovaries in postmenopausal
women does not affect GnRH-induced gonadotrophin
secretion in the short term. It is suggested that the
postmenopausal ovary is not a dominant regulator of
hypothalamic–pituitary interactions.
During the normal menstrual cycle, ovarian steroids are im-
portant regulators of pituitary function. Oestradiol (E2) exerts a
negative effect on basal gonadotrophin secretion, while at the
same time sensitizes the pituitary to GnRH (Lasley et al ., 1975;
Wang et al ., 1976; Messinis et al ., 1998). The interaction
between E2 and GnRH during the follicular phase of the cycle
results in the positive feedback effect which results in the
midcycle endogenous LH surge (Hoff et al ., 1977). Following
the menopause, serum concentrations of ovarian hormones
become very low, while those of FSH and LH increase markedly
(Burger, 1996).
In terms of stimulation by GnRH, an enhanced response of
LH and FSH to this peptide has been reported in postmenopausal
women (Siler & Yen, 1973) that can be modulated by the admin-
istration of exogenous oestrogen (Yen et al ., 1974; Lasley et al .,
1975). Although this denotes the crucial role of the ovaries on
hypothalamic–pituitary interaction during the reproductive
years, no studies have been performed to investigate if GnRH-
induced gonadotrophin secretion after menopause is still under
the ovarian control. In premenopausal women, the use of the
model of ovariectomy has provided useful information regarding
the relationships between the ovaries and the hypothalamic–
pituitary system during the normal menstrual cycle (Yen & Tsai,
1971; Alexandris et al ., 1997; Messinis et al ., 2002). So far in
postmenopausal women, only basal gonadotrophin secretion
has been sporadically examined following ovariectomy (Heinonen
et al ., 1986; Hughes et al ., 1991).
The present study was undertaken to investigate changes in
basal and GnRH-stimulated gonadotrophin secretion during the
immediate period after ovariectomy in postmenopausal women
in order to clarify whether their ovaries are still playing an endo-
crine role within the reproductive axis.
Correspondence: Professor I. E. Messinis, Department of Obstetrics and
Gynaecology, University of Thessalia, 22 Papakiriazi Street, 41222
Larissa, Greece. Tel.: + 302410682795; Fax: + 302410670096;
E-mail: messinis@med.uth.gr