Newer
Older
ez-indexation / app / public / data / in / corpus / 0D3D6D46102A83283FF3D83AFE53C471C95874B5.txt
@kieffer kieffer on 7 Mar 2017 19 KB v0.0.0
Maturitas 29 (1998) 133 – 138

The effect of hysterectomy and endometrial ablation on follicle
stimulating hormone (FSH) levels up to 1 year after surgery
J.G.M. Derksen a, H.A.M. Brolmann b,*, M.A.H.M. Wiegerinck b, H.L. Vader c,
¨
A.P.M. Heintz a
b

a
Department of Obstetrics and Gynecology, Uni6ersity Hospital, Utrecht, The Netherlands
Department of Obstetrics and Gynecology, Sint Joseph Hospital, P.O. Box 7777, 5500 MB Veldho6en, The Netherlands
c
Department of Clinical Chemistry, Sint Joseph Hospital, Veldho6en, The Netherlands

Received 16 October 1997; received in revised form 28 January 1998; accepted 30 January 1998

Abstract
Objecti6es: In this study the hypothesis was tested, that in premenopausal patients FSH-levels would rise after
‘simple hysterectomy’. As endometrial ablation is not supposed to compromise ovarian bloodflow, there would be no
such change in ablated patients. Methods: Between January 1995 and April 1996, consecutive premenopausal patients
with dysfunctional uterine bleeding who were scheduled for hysterectomy or endometrial ablation were asked to
participate in the study. Bloodsamples were drawn before surgery, six weeks, six months and one year after surgery.
FSH and oestradiol (E2) were assayed. In all patients data about length and weight were collected to calculate Body
Mass Index (BMI). Every visit patients filled in a questionnaire, containing questions about typical climacteric
complaints, combined in a five-point scale. Results: Except for a significant difference in preoperative FSH-level
between both groups, there were no significant differences regarding age, Body Mass Index (BMI), oestradiol (E2) or
the percentage of women with vasomotor complaints. Compared to the preoperative starting level, six weeks, six
months and one year after surgery a significant rise in serum FSH in the hysterectomy group, as well as in the
ablation group was found. However there was no significant difference in FSH increase between both groups. One
third of the patients in both groups had typical climacteric complaints as flushing and nocturnal sweating.
Conclusions: Assaying serum FSH-levels before and after uterine surgery and comparing hysterectomized patients and
patients after endometrial ablation, we found a significant rise in FSH-level up to one year after surgery in both
groups postoperatively, indicating impaired ovarian function. There was no difference in FSH-levels between both
groups.Therefore major uterine surgery (hysterectomy, ablation) may prelude an earlier onset of menopause. © 1998
Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Hysterectomy; Endometrial ablation; Ovarian function; Menopause

* Corresponding author. Tel.: +31 40 2588385; fax: +31 40 2588387.
0378-5122/98/$19.00 © 1998 Elsevier Science Ireland Ltd. All rights reserved.
PII S0378-5122(98)00018-8

134

J.G.M. Derksen et al. / Maturitas 29 (1998) 133–138

1. Introduction
Hysterectomy is one of the most frequently
performed major operations in Western countries. Common indications to perform a hysterectomy
are
uterine
leiomyomas
(30%),
dysfunctional uterine bleeding (20%), endometriosis and adenomyosis (20%), genital prolaps (15%) and malignant conditions of the
uterus [1]. The majority of the patients is premenopausal at the time of hysterectomy. In case
of dysfunctional uterine bleeding alternative surgical treatments are available like hysteroscopic
electroresection of the endometrium or other
forms of ablative therapy. Endometrial ablation
is considered to be a cost-effective therapy with
satisfaction rates of 70 – 90%, while preserving
the uterus [2]. Evidence that a simple hysterectomy may harm ovarian function is increasing
but still circumstantial [3 – 8] and results are
sometimes
controversial
[9,10].
Increased
boneloss after premenopausal hysterectomy is reported [11] as well as cardiovascular disease [12],
both conditions associated with ovarian failure.
By blocking the circulation of the uterine vessels,
hysterectomy can reduce ovarian bloodflow [13],
which may result in loss of follicular reserve [7]
and premature menopause [5]. Follicle stimulating hormone (FSH), being a gonadotropic hormone, is a marker of ovarian failure [14].
However most studies are cross-sectional [6,15]
and longitudinal studies in hysterectomized patients are lacking.
In this study the hypothesis was tested, that in
premenopausal patients FSH would rise after
‘simple’ hysterectomy. As endometrial ablation is
not supposed to harm ovarian bloodflow, there
would be no such change in ablated patients.

2. Materials and methods
Between January 1995 and April 1996 consecutive premenopausal patients with menstrual disorders (menorrhagia, dysmenorrhoea due to
endometriosis, adenomyosis and leiomyomatosus) and genital prolaps who were scheduled for
hysterectomy or endometrial ablation were asked

to participate in our study. Ethical committee
approval for research and written informed consent in all patients was obtained. The premenopause was defined by a regular menstrual
cycle. Excluded were patients older than 49 years
of age, patients with a preoperative FSH \ 15
IU/l and patients who had one or both ovaries
removed in the past or in the present hysterectomy, e.g. women with malignant conditions of
the uterus. All patients were operated on by the
same surgical team, using similar operative techniques in the different procedures. In the hysterectomy group (n = 65) simple abdominal
hysterectomy (n= 20), vaginal hysterectomy (n=
26), laparoscopically assisted vaginal hysterectomy (LAVH) (n= 13) and laparoscopically
assisted supravaginal hysterectomy (LASH) (n=
6) were performed. In the group women treated
with endometrial ablation (n= 23) electroresection of the endometrium (n = 5) and endometrial
ablation with the hot fluid balloon (ThermaChoice, Gynaecare, CA) (n = 18) were performed.
None of the entered patients received any type
of steroid treatment in the postoperative period.
Bloodsamples were drawn irrespective of the
menstrual cycle before surgery, 6 weeks, 6
months, and 1 year after surgery. Follicle stimulating hormone (FSH) and oestradiol (E2) were
assayed. FSH was measured in serum by an immunometric sandwich technique (Amerlite). The
mean FSH-value and reference interval (9 2
standard deviations) in our laboratory for premenopausal women is 3.3 IU/l (0.7–7.9). The
maximum value for the midcycle FSH-value is
12.3 IU/l. Oestradiol was measured with a direct
radio-immunoassay technique (clinical assays).
Simultaneously patients completed a questionnaire, containing questions addressing vasomotor
complaints and vaginal dryness scored in a fivepoint scale according to Oldenhave [8]. These
complaints were labeled ‘typical’ climacteric complaints. In all patients data were collected about
length and weight to calculate the Body Mass
Index (BMI). There were 109 patients, who entered the study. Due to drop out, which is explained in detail later, data of 88 patients were
available for further analysis.

J.G.M. Derksen et al. / Maturitas 29 (1998) 133–138

135

Table 1
Characterisitics in premenopausal patients in the hysterectomy group (n = 65) and the endometrial ablation group (n =23)
Hysterectomy (n= 65)
Age in years (S.D.)
Body Mass Index (S.D.)
Preop FSH IU/l (S.D.)
Preop oestradiol (S.D.)
Preop vasomotor symptoms

Endometrial ablation (n =23)

P

40.8 (4.2)
24.2 (4.4)
3.8 (2.4)
0.25 (0.24)
5/65 (8%)

40.6 (5.5)
24.1 (4.4)
4.8 (2.2)
0.30 (0.26)
2/23 (9%)

NS**
NS
0.03 *
NS
NS

* After log transformation to normal probability plots.
** Not significant.

2.1. Statistics
The data were analyzed statistically by the
(Yates corrected) Chi-square test and t-test for
independent or paired samples. Skewed data were
transformed logarithmically to normal distributions (normal probability plot). A P value B 0.05
was considered to indicate statistically significant
difference.

3. Results
Between January 1995 and April 1996, 109
patients underwent hysterectomy or endometrial
ablation and entered the study. In three patients,
unexpected adnexal surgery, on ovarian or
fallopian tube, was performed. In three patients,
hysterectomy was performed because of persistent
vaginal bloodloss after an ablative procedure
within one year after the initial surgical procedure
and 14 patients were lost to follow-up due to non
responding. In 89 patients, the data in four points
of time were complete. After exclusion of one
patient with a preoperative FSH of 24 IU/l, the
data of 88 patients were available for further
analysis.
There was a slight but statistically significant
difference in preoperative FSH-levels between
both groups. Age, Body Mass Index (BMI),
oestradiol (E2) or the percentage of women with
typical climacteric complaints was not statistically
different between the groups (Table 1).
Compared to the preoperative level, 6 weeks, 6
months and 1 year after surgery, a significant rise
in serum FSH was found in the hysterectomy

group, as well as in the ablation group (Fig. 1).
Patients with a preoperative FSH-level \ 15 IU/l
were excluded. Six weeks after surgery 10% (9/88)
of the other women had a serum level FSH \ 15
IU/l, after 6 months 8% (7/88) and 1 year postoperatively 10% (9/88) (Table 2). These changes
were not statistically different and did not differ
according to the type of surgery. Less than half of
the women with FSH-values more than 15 IU/l
complained of flushing and sweating. Within the
first half-year postoperatively, a significant rise in
E2 was detected in the hysterectomy group. In the
smaller ablation group, the same trend was seen
but was not significant (Fig. 2). No differences in
hormonal levels in the postoperative period between patients after hysterectomy and endometrial ablation could be detected.
Power analysis shows that only a difference in
FSH-level of 4 IU/l or more can be detected with
a power (1-beta) of 80%, alpha being 95% in a
sample of 90 patients.
Although only patients with a preoperative
FSH-level B 15.1 IU/l were included, 7.7% (5/65)
in the hysterectomy group complained of moderate to severe flushing and sweating before operation. In the hysterectomy group these numbers
were 6 weeks, 6 months and 1 year after surgery
7.7% (5/65), 17% (11/65) and 17% (11/65), in the
ablation group 13% (3/23), 17.4% (4/23) and 8.7%
(2/23), respectively.

4. Discussion
In the current study in premenopausal patients,
we found a statistically significant rise in serum-

136

J.G.M. Derksen et al. / Maturitas 29 (1998) 133–138

Fig. 1. Median FSH levels, 5, 25, 75, and 95 percentiles before and after hysterectomy with ovarian preservation and endometrial
ablation. FSH levels of hysterectomized patients (n = 65) AB, AC, AD: PB0.01, CD: P B 0.05. Ablated patients (n = 23): AB, AC,
AD: P B 0.05. t-Test after log-transformation to normal probability plot.

FSH and E2 6 weeks, 6 months and 1 year after
uterine surgery, comprising hysterectomy as well
as endometrial ablation compared to preoperative
values.
From 6 weeks on serum-FSH- and E2-levels
did not change significantly up to one year after
surgery. An ‘acute effect’ on the ovaries left in situ
within one week after simple hysterectomy, was
already established in a longitudinal study [3].
After vaginal or abdominal hysterectomy a significant decrease in the peripheral levels of circulating
steroids (E2 and progesterone) was seen, as well in
the proliferative phase as in the luteal phase in
comparison to the same measurements after a
mere diagnostic laparoscopy. In most patients the
decrease was more apparent in the second postoperative day and lasted for more than three days.
However, serum FSH-levels, obtained daily, failed
to show any significant short term change compared to preoperative values. In an other longitudinal study the sex-hormonal profile was assayed
in premenopausal patients [16]. Patients who had
both ovaries preserved at hysterectomy, were
compared to patients, in whom a unilateral
oophorectomy was performed at hysterectomy.
Before the operation ovarian function was evaluated by measuring FSH, LH and E2. This was

repeated at regular intervals until 6 months postoperatively. The ‘acute effect’ (decrease of E2
within the first week postoperatively) of hysterectomy on ovarian function was confirmed, but also
a steady rise of the gonadotropins in the first half
year after unilateral oophorectomy was shown. In
patients with both ovaries preserved at hysterectomy, no such changes in gonadotropic hormones
were seen.
In cross-sectional studies hypergonadotropism
was found in hysterectomized premenopausal
women [6]. These findings were related to a higher
incidence of climacteric symptoms after hysterectomy [8] and an earlier menopause [5]. In an
elegant peroperative experiment, using a 133Xenon clearance technique in five women before
and immediately after abdominal hysterectomy,
Janson et al. could demonstrate an acute reduction of ovarian bloodflow, immediately after ligation of the uterine vessels [13]. He assumed this
reduction in bloodflow was responsible for the
‘steroid drop’ after hysterectomy.
In the current study a possible confounding
effect of the high midcyclic FSH-values is ruled
out by setting the cut-off level at 15 IU/l (Table
2). This value exceeds the maximum value in our
laboratory for the midcycle peak level of FSH

J.G.M. Derksen et al. / Maturitas 29 (1998) 133–138

137

Table 2
Patients with postoperative FSH levels up to 15 IU/l or more, according to type of surgery, as well as the portion of patients with
vasomotor symptoms
Time after surgery

FSH \15 IU/l after hysterectomy (n= 65)

FSH \15 IU/l after endometrial ablation (n =23)

6 Weeks (%)
with VMSa (%)
6 Months (%)
with VMS (%)
1 year (%)
with VMS (%)

6/65 (10%)
1/6 (16%)
5/65 (8%)
0
7/65 (11%)
2/7 (28%)

3/23 (13%)
1/3 (33%)
2/23 (8.7%)
0
2/23 (8.7%)
1/2 (50%)

a

VMS, vasomotor symptoms.

(12.3 IU/l). As all samples were randomly drawn
in the menstrual cycle, it is unlikely that a larger
proportion of women is midcyclic on three separate occasions after the operation — thus explaining the higher mean FSH levels — than before.
An unexpected the finding was the equal rise of
FSH level after the operation in both hysterectomized and ablated patients. A paracrine effect
of the endometrium on the ovarium function, as
seen in rabbits is often suggested, but never scientifically substantiated in humans. On the other
hand, one can speculate, that also after endometrial ablation in some way the uterine and thereby
the ovarian bloodflow is reduced, resulting in an
‘acute effect’, described by Stone [3]. To proof a

relationship of uterine surgery and a rise of the
FSH levels, participation of a control group without uterine surgery should be appropriate.
How to explain the possible longer term effects
of hysterectomy on the ovaries, which are clearly
demonstrated in the pathological anatomical
study of Souza et al. [7]. He biopsied the ovaries
of premenopausal women during abdominal hysterectomy and one year later at laparoscopy. Besides thickening of the tunica albuginea and
stromal hyperplasia, the ovarian histology one
year after hysterectomy showed an impressive reduction of follicular reserve (standardized count
at magnification of × 25 decreased from 7.8 to
1.0). As follicular depletion and a compromised

Fig. 2. Median oestradiol (E2) levels 5, 25, 75, and 95 percentiles before and after uterine surgery. E2 levels of hysterectomized
patients (n = 65): AB, AC: PB 0.05. AD: P= 0.08. Changes in E2-levels of ablated patients (n = 23) were not significant. t-Test after
log-transformation to normal probability plot.

138

J.G.M. Derksen et al. / Maturitas 29 (1998) 133–138

ovarian response can stimulate the hypophysis to
produce FSH (which explains the rise of FSH-levels), FSH itself may stimulate a greater proportion of the primordial follicles entering the
growing pool, as is demonstrated in rats [17],
resulting in higher E2-levels. This autocatalytic
process accelerates follicular depletion and results
ultimately in ovarian exhaustion and declining
E2-levels. It is therefore plausible that a postoperative rise in FSH-levels is associated with earlier
menopause.
In the current study, 11% (7/65) and 9% (2/23)
of the patients 1 year after hysterectomy and
endometrial ablation, respectively, had FSH-levels
\ 15 IU/l, showing declining follicular reserve.
Only one third of them had typical climacteric
complaints as flushing and sweating. The missing
correlation between hormone values and the presence or severity of vasomotor complaints is well
established [8]. Bearing in mind the increased risk
of ostopenia and cardiovascular disease after hysterectomy and the absence of the climacteric signal of irregular menses, a prospective study of the
possible benefits of hormonal screening after premenopausal hysterectomy and, in case of amenorrhoea, after premenopausal endometrial ablation
is recommended.

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

Acknowledgements
We would like to thank L. Hansen MD for
helping collecting the data and B.W. Mol for
critically reading the manuscript.

[14]

[15]
[16]

References
[1] Carlson KJ, Nichols DH, Schiff I. Indications for hysterectomy. N Engl J Med 1993;328:856–60.
[2] Pinion SB, Parkin DE, Abramovitch DR, Naji A, Alexander DA, Russell IT, Kitchener HC. Randomised trial
of hysterectomy, endometrial laser ablation and transcer-

[17]

.

vical endometrial resection for dysfunctional uterine
bleeding. Br Med J 1994;309:983 – 97.
Stone SC, Dickey RP, Mickal A. The acute effect of
hysterectomy on ovarian bloodflow. Am J Obstet Gynecol 1975;121:193 – 7.
Riedel HH, Lehmann-Willenbrock E, Semm K. Ovarian
failure fenomena after hysterectomy. J Reprod Med
1986;31:597 – 600.
Siddle N, Sarrell P, Whitehead M. The effect of hysterectomy on the age at ovarian failure: identification of a
subgroup of women with premature loss of ovarian function and literature review. Fertil Steril 1987;47:94 – 100.
Kaiser R, Kusche M, Wurz H. Hormone levels in women
after hysterectomy. Arch Gynecol Obstet 1989;244:169 –
73.
Souza AZ, Fonseca AM, Izzo VM, Clauzet RM, Salvatore CA. Ovarian histology and function after total abdominal hysterectomy. Obstet Gynecol 1986;68:847.
Oldenhave A, Jaszmann LJ, Everaerd WT, Haspelss AA.
Hysterectomized women with ovarian conservation, report more severe climacteric complaints than do normal
climacteric women of similar age. Am J Obstet Gynecol
1993;168:765 – 71.
Ravn P, Lind C, Nilas L. Lack of influence of simple
premenopausal hysterectomy on bonemass and bone
metabolisme. Am J Obstet Gynecol 1995;172:891 – 5.
Metcalf MG, Braiden V, Livesey JH. Retention of normal
ovarian function after hysterectomy. J Endocrinol
1992;135:597 – 602.
Watson NR, Studd JWW, Garnett T, Savas M, Milligan
P. Boneloss after hysterectomy with ovarian conservation.
Obstet Gynecol 1995;86:72 – 7.
Ritterband AB, Jaffe IA, Denson PM, Magagna PF,
Reed E. Gonadal function and the developement of coronary heart disease. Circulation 1963;27:237 – 51.
Janson PO, Janson I. The acute effect on ovarian blood
supply. Am J Obstet Gynecol 1977;127:349 – 52.
Lee SJ, Lenton EA, Sexton L, Cooke ID. The effect of
age on cyclical patterns of plasma LH, FSH, oestradiol
and progesterone in women with regular menstrual cycles.
Hum Reprod 1988;3:851 – 5.
Seeley T. Oestrogen replacement therapy after hysterectomy. Br Med J 1992;305:811 – 2.
Bukovski I, Halperin R, Schneider D, Golan A, Hertzianu I, Herman A. Ovarian function followingabdominal
hysterectomy with and without unilateral ooforectomy.
Eur J Obstet Gynaecol Reprod Biol 1995;58:29 – 32.
Richardson SJ, Senikas V, Nelson JF. Follicular depletion during the menopausal transition: evidence accelerated loss and ultimate exhaustion. J Clin Endocrin Metab
1987;65:1231 – 7.

.