Uterine Disorders
the proportion of hysterectomised women with hormonal levels in the post-menopausal range or to compare mean or median levels between women with and without hysterectomy.22–26
The largest of
these studies was a cross-sectional analysis of data from 1,716 women aged 35–49 years who participated in the US National Health and Examination Survey.26
As compared with women with
intact uteri and ovaries, women with a hysterectomy only or hysterectomy plus unilateral oophorectomy were statistically significantly more likely to have elevated FSH levels (>20 international units/litre [IU/l]), with odds ratios of 1.5 (95 % confidence interval [CI] 1.0–2.5) and 2.4 (95 % CI 1.3–4.6), respectively.
Stronger evidence for evaluating the risk of ovarian failure after hysterectomy has come from studies that used prospective study designs and determined menopause status on the basis of hormonal measurements.27–36
However, even within this group of studies, the interpretation of the findings must take into consideration the sample size, length of follow-up and control group.
The prospective study with the largest sample of women with hysterectomy (n=531) and the longest duration of follow-up (10 years) did not include a comparison group of women without hysterectomy.32 The authors reported that ovarian failure, defined as an FSH level >30 IU/l, occurred in 21 % of the women with abdominal hysterectomy and in 28 % of those with vaginal hysterectomy. The median age at ovarian failure was 47 years. Although the authors concluded that early ovarian failure among women with hysterectomy was not confirmed in their study, the lack of a control group makes their conclusions rather tenuous, especially since the median age at ovarian failure in the study population is considerably lower than most population estimates of median age at menopause.
Other prospective studies have compared women undergoing hysterectomy with women having either uterine artery embolisation or endometrial ablation.27–30,34,36
Each of these studies was relatively
small, with sample sizes of women with hysterectomy ranging from 15 to 89, and a duration of follow-up ranging from six months to two years. Although some of the studies reported increases in FSH after hysterectomy, none found statistically significant differences in mean FSH levels or the proportion of women with FSH values >40 IU/l between the hysterectomy group and the comparison group. While these studies did not provide evidence of increased risk of ovarian failure after hysterectomy, it is unclear whether this reflects their limited statistical power, the relatively short duration of follow-up or the possibility that the procedures used in the comparison groups also had an effect on ovarian function.
The strongest evidence for an increased risk of earlier ovarian failure after hysterectomy comes from two prospective cohort studies, each of which compared women undergoing hysterectomy with a group of normal controls with intact uteri and ovaries.33,35
The study conducted
in New Zealand included 257 women with hysterectomy and 259 controls,33
Both
and the study conducted in the US (North Carolina) included 407 women with hysterectomy and 465 controls.35
studies followed their cohorts for up to five years and categorised women as having ovarian failure if FSH values were ≥40 IU/l. Farquhar and colleagues reported that ovarian failure occurred in 21 % of women in the hysterectomy group compared with 7 % of women in the control group over the five years of the study.33
They further estimated that women with hysterectomy reached menopause 3.7 years 36
(95 % CI 1.5–6.0) earlier than women in the control group. Moorman and colleagues reported similar findings, although the magnitude of the associations was not quite as strong.35
The hazard ratio for ovarian
failure among women with hysterectomy as compared with controls was 1.92 (95 % CI 1.29–2.86), and it was estimated that ovarian failure occurred 1.88 years earlier among the women with hysterectomy. The Kaplan–Meier plot comparing the time to ovarian failure in the hysterectomy and control groups suggested that there is not an abrupt disruption of ovarian function after hysterectomy, but rather a consistent increase in the risk of ovarian failure over time. Both studies reported that the risk of ovarian failure was higher for women who had a unilateral oophorectomy along with their hysterectomy compared with women with both ovaries left intact. It is also noteworthy that the effect of hysterectomy on estimated age at ovarian failure was at least as strong as cigarette smoking – the strongest non-genetic predictor of age at menopause.37–39
Mechanisms of Ovarian Failure After Hysterectomy
the causal pathway remains unclear. One of the most prominent hypotheses suggests that the surgery compromises blood flow to the ovaries, resulting in reduced production of hormones and earlier ovarian failure.21
The evidence for this is mixed,
Another hypothesis is that the uterus has an inhibitory influence on pituitary FSH secretions and consequently has an effect on follicular atresia.45
with some but not all studies finding reduced ovarian blood flow after hysterectomy.40–44
It is posited that the removal of the
uterus allows FSH levels to rise and accelerates follicular depletion, leading to earlier menopause.
An alternative possibility is that it is not the surgery itself, but the underlying condition leading to hysterectomy that puts women at increased risk of earlier ovarian failure. Common indications for hysterectomy, such as leiomyomas, endometriosis or dysfunctional uterine bleeding, could be associated with a risk of earlier menopause, but there are scant data available to address this hypothesis. It is possible that, in some cases, the excessive uterine bleeding leading to hysterectomy is a more extreme manifestation of the change in menstrual bleeding patterns that many peri-menopausal women experience. Whether there is relationship between other indications for hysterectomy, such as leiomyomas or endometriosis, and age at ovarian failure is unknown. Studies reporting higher bone density in women with leiomyomas provide indirect evidence of higher oestrogen levels and, by extension, higher ovarian function in these women, which argues against leiomyomas being a risk factor for earlier menopause.46,47
Distinguishing whether ovarian failure after hysterectomy is due to the surgery itself or the underlying condition leading to surgery is a question with high clinical relevance, but one that cannot be answered with the available evidence. Each of the large prospective studies that evaluated ovarian function after hysterectomy in comparison with normal controls utilised FSH levels ≥40 IU/l as a marker of ovarian failure, but acknowledged the limitations of FSH as a marker of ovarian failure.33,35
While FSH is the most commonly used indicator of ovarian failure in the menopause literature, it is recognised that there is no cut-point that absolutely distinguishes pre- and
EUROPEAN OBSTETRICS & GYNAECOLOGY
While results from two prospective studies with long-term follow-up and a comparison group of normal controls provide compelling evidence of earlier ovarian failure among women undergoing hysterectomy,33,35
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