Download Table 1. Annual Incidence of ovarian cancer by age group

Ovarian Conservation at the Time of
Hysterectomy for Benign Disease
Clinical Obstetrics and Gynecology
Vol.50 / Number 2 / June 2007
Abstract
Benefits of The Postmenopausal Ovary
Our Study Design
Our Study Results
Comment
Criticisms and Answers
Conclusions
Abstract
Prophylactic oophorectomy when hysterectomy
: 78% ( 45 ~ 64 years old)
Ovary (after menopause)
: continues to produce androstenedione and testosterone
androgens
converted in fat, muscle, and skin
estrone
Oophorectomy
: risk of coronary heart disease (CHD) and osteoporosis ↑↑
Cause of Death
ovarian cancer - 14,000 / year
heart disease - 490,000 / year
within 1 year after hip fracture - 48,000 / year
Abstract
Study Design
PubMed and the Cochrane database
- the incidence of disease and mortality from conditions that
seem to be related to ovarian hormones
: CHD, ovarian cancer, breast cancer, stroke and hip fracture
- data for death from all other causes
The model
hypothetical cohort of 10,000 women undergoing hysterectomy and
who chose oophorectomy (vs. ovarian conservation) between the ages
of 50 and 54 [without estrogen therapy(ET)], that by the time they
reach age 80
women will have died from ovarian cancer < 47
women will have died from CHD > 838
women will have died from hip fracture > 158
Abstract
the decision to perform prophylactic oophorectomy
should be approached with great caution for the majority
of women who are at low risk of developing ovarian
cancer
Introduction
the percentage of hysterectomies + bilateral oophorectomies
25% (1965)→ 55% (1999) (more doubled )
78% : concurrent oophorectomy between ages 45 ~ 64
(recent data from the CDC show that)
Ovarian cancer
diagnose before it has metastasized : hard
late stage disease : associated with a high mortality
relatively uncommon malignancy
(if women with known BRCA 1 or 2 germ-line mutations or
from high-risk families are excluded)
Table 1. Annual Incidence of ovarian cancer by age group
Introduction
Cause of Death
ovarian cancer : 14,000 women, every year
lung cancer : 70,000 women
colon cancer : 28,000 women
breast cancer : 40,000 women
heart disease : 490,000 women
within 1 year after hip fracture : 48,000 women
Benefits of preserving ovarian function
risks of coronary heart disease (CHD)
osteoporotic fracture
Benefit of the Postmenopausal Ovary
Ovaries produce
reproductive years : estradiol, testosterone, androstenedione
after menopause : androstenedione, testosterone (until age 80)
androgens
converted in fat, muscle, and skin
estrone
After oophorectomy, menopausal women
: significantly lower plasma levels of androstenedione and
testosterone than naturally menopausal women.
Benefit of the Postmenopausal Ovary
Oophorectomy - the risk of cardiovascular disease ↑↑
Oophorectomy after age 50
the risk of developing a first MI by 40% ↑
[relative ratio 1.4, confidence interval (CI) 1.0-2.0]
Hysterectomy with oophorectomy
an independent predictor of Framingham risk of myocardial
infarction or coronary death
- Data from the Women's Health Initiative (WHI)
Autopsy in women with prior bilateral oophorectomy
more severe coronary atherosclerosis
earlier menopause (natural or surgical)
associated with more subclinical atherosclerosis
Benefit of the Postmenopausal Ovary
Oophorectomy - the risk of osteoporosis ↑↑
estrogens and androgens : bone resorption↓
androgens : bone formation ↑
postmenopausal state at the time of oophorectomy
: osteoporotic fractures > 54% than women with intact ovaries
- One study found that after 16 years of follow-up (median)
≥ 60 years old
: 2-fold increase in mortality after low trauma hip fractures
Our Study Design
PubMed and the Cochrane database
Incidence of disease and mortality from 5 conditions
: related to ovarian hormones
- CHD, ovarian cancer, breast cancer, stroke and hip fracture
data for death from all other causes
articles that investigated the relative risk of developing these 5
conditions for generally healthy women having a hysterectomy with
either oophorectomy or ovarian conservation between the ages of
40 and 75.
Our Study Design
Risk of Ovarian cancer
After hysterectomy
: reduce by an average of 46%
< Theories to explain the decreased risk >
prohibiting reflux of carcinogens (endometrial tissue, HPV, or talc)
through the reproductive tract to the ovaries
destruction of reproductive tract tissue with release of antigens
cause the formation of antibodies (MUC 1) to ovarian cancer cells
After bilateral oophorectomy
: 0%
Our Study Design
Risk of myocardial infarction
up to age 55
: double the baseline risk (relative ratio=2.2 CI 1.2-4.2)
ages 55 ~ 65
: the risk of CHD was found to decrease 6% for each year
oophorectomy is delayed after menopause
> 65 years old
: the relative risk of MI 1.0 (d/t no applicable data)
Our Study Design
Risk of osteoporotic fracture
after age 49
: 50% increased risk of hip fracture
after age 60
: 2-fold in mortality ↑ after low trauma hip fractures
- a prospective cohort study (OR 2.18, CI 2.03-2.32)
after hip fracture
60 ~ 64 : lost 11 years of life
70 ~ 74 : lost 4.4 years
Our Study Design
Risk of breast cancer
age < 50
: 50% reduction in for 10 years after the surgery
age > 50
: no reduction in risk
Our Study Results
Figure I. Risk of death by age 80 for non-ET users as a function of age at oophorectomy with 95%
confidence interval
Our Study Results
ages 50 to 54 with hysterectomy
- average risk of ovarian cancer, CHD, osteoporosis, breast cancer,
and stroke the probability of surviving to age 80
ovarian conservation : 62.46%
oophorectomy
: 53.88%
→ 8.58% difference in survival
- fewer women dying of CHD (15.95% vs. 7.57%)
- hip fracture (4.96% vs. 3.38%)
age 55 ~59
- the survival advantage : 3.92%
after age 64
- no significant difference in survival
Our Study Results
Sensitivity analyses were performed and no
analysis showed that oophorectomy
improved survival
Our Study Results
For a hypothetical cohort of 10,000 women undergoing hysterectomy
and who chose oophorectomy (vs. ovarian conservation) between the
ages 50 and 54 (without ET), our analyses predict that by the time
they reach age 80,
Ovarian cancer : < 47 women will have died
CHD : ≥ 838 women will have died
hip fracture : ≥ 158 women will have died
→ oophorectomy
: leads to an overall excess mortality of 858 / 10,000 women in
this age group.
Comment
Heart disease : relatively common cause of death
Ovarian cancer : uncommon
→ benefit to ovarian conservation at the time of hysterectomy for
benign disease (not at high risk of ovarian cancer)
Comment
Oophorectomy
Age < 65 : the risk of dying from CHD ↑
Age > 65 : mortality primarily due to hip fracture ↑
in premenopausal, and some postmenopausal women
: lead to the sudden onset of hot flushes, mood disturbances
Other problems
- a decline in a sense of well-being
- a decline in cognitive functioning
- poor sleep quality, depression
- a decline in sexual desire
- frequency
Criticisms and Answers
I. Use of the Nurse's Health Study data (because it was observational)
→ study followed 121,700 women over 6 years and remains the
largest database available for analysis
II. opinion that we should not have included the oophorectomy and
no ET arm in our study, because this choice should be
unacceptable to gynecologists
→ clearly the most common situation found clinically
Criticisms and Answers
III. Oophorectomy be performed as prophylaxis for the future
possibility of pelvic pain, residual ovary syndrome, mild
endometriosis, or ovarian cyst formation
→ among 2561 women having a hysterectomy without oophorectomy
for any indication and followed for 20 years, subsequent
oophorectomy - performed in just 2.8%
Criticisms and Answers
IV. There were many risk factors for disease and mortality
(menopausal status, age, lipoprotein patterns, gallbladder
disease, venous thromboembolism and colon cancer, etc) that
our model did not take into account
→ we purposely constructed the model without too much
complexity by choosing the 5 conditions most commonly
associated with oophorectomy.
→ On the basis of our sensitivity analyses, it is unlikely that these
factors would influence the outcome of our study.
Criticisms and Answers
approximately 300,000 US women
: incidental oophorectomy annually
→ based on one factor alone - the risk and fear of ovarian cancer
: inappropriate
risk of ovarian cancer
: has been overemphasized by physicians to the exclusion of
other long-term risks of estrogen deficiency
raise awareness among women and their gynecologists regarding the
public health consequences of routinely performed
oophorectomy.
Conclusions
Prophylactic oophorectomy
: approached with great caution for the majority of women
at low risk of developing ovarian cancer
< age of 65
“the decision to perform prophylactic oophorectomy
: based on
the patient's age
other factors that weigh individual risk for developing ovarian
cancer against loss of ovarian function.”
- recommended by Clinical management guidelines published by the American College of
Obstetricians and Gynecologists in 1999 –
Next
Criticisms and Answers
In 1999, before publication of the WHI, and “at a time when medical
support for ET and publicity for ET were high,” only 31% of women
continued to use ET for 5 years or longer after hysterectomy and
oophorectomy.
And, in the 6 months after publication of the WHI continuation rates
of ET decreased from 12.6% to 9.1% and new starts also decreased
significantly.
In women with documented osteoporosis and beginning treatment
with either ET, estrogen and progestin, bisphosphonates or
raloxifene (n=58,109) medication continuation rates were less than
25% at 12 months.
Likewise, statin continuation rates are 18% at the end of 1 year.
Criticisms and Answers
Women may have side effects, cost-related issues, or fears and
belief systems about medications that preclude use despite a
physician's recommendation.
Furthermore, none of these studies account for women who never
see a doctor, or who never get a prescription, or who get a
prescription but choose not to fill it and they, therefore,
underestimate the subsequent risk of untreated disease for large
numbers of women.
Consequently, the assumption that medical treatment can
ameliorate these conditions after oophorectomy is not convincing.
Criticisms and Answers
V. “it is hard to believe that estrogens are more dangerous than
conserved ovaries” and pleaded for oophorectomy.
We wonder what ever happened to the concept of “evidence” and
the principle “first, do no harm”?
Estrogens in women:
In women, estrogens normally exist in approximately the following
ratio:
Estriol 60-80%
Estradiol 10-20%
Estrone 10-20%
it was generally believed that the decreased incidence of CHD in
women before menopause was mediated by a protective effect of
estrogen on the coronary arteries, achieved by modulating levels of
serum cholesterol.4 However, other research suggests that estrogeninduced improvements in serum cholesterol account for only one third
of the observed clinical benefits of estrogen.
It was hypothesized that an atheroprotective effect of estrogen may be
mediated by this hormone’s direct effect on vascular smooth muscle
cells.
In fact, the data show that estrogen can increase dilation of arteries
and inhibit the response of blood vessels to injury and the
development of atherosclerosis.
relationship between androgen levels and CHD in women.
The idea that DHEA protects against atherosclerosis was
proposed by Kask in 1959.
Some data show that serum dehydroepiandrosterone sulfate
(DHEA-S) and androgen levels decline with age, and that levels
in the normal physiological range are correlated with lower risk
of carotid artery atherosclerosis.
There is growing support for a possible benefit of DHEA
supplementation in preventing cardiovascular events in women,
predominantly through an estrogenic effect.
Testosterone can regulate vascular physiology directly
through stimulation of androgen receptors and inhibition of
plaque formation, and indirectly after conversion to estradiol.
Nevertheless, evidence concerning the efficacy of DHEA and
testosterone in protecting the cardiovascular system remains
inconclusive and warrants further study.
Our study has several weaknesses.
The probability estimates were derived from mostly case-control
studies, with the inherent weaknesses of selection bias, reporting
bias, and chance.
Our study combines the data from different studies and disparate
populations, but to date no large cohort study has examined all of
these outcomes in the same population.
Subjects for most selected studies were predominantly white and
further study is needed to confirm these estimates for non-white
women.