Clinical Pearls:
- Women who had bilateral oophorectomy before menopause experienced increased risk of depression, hyperlipidemia, cardiac arrhythmias, coronary artery disease, arthritis, asthma, chronic obstructive pulmonary disease, and osteoporosis. (hazard ratio, 1.22; 95% CI, 1.14-1.31; P<.001).
- The younger the age at oophorectomy, the stronger the association with these chronic conditions.
- In these group of women, the risk of occurrence of many chronic condition was reduced by supplementing estrogen therapy.
- Study provides definitive evidence against use of bilateral oophorectomy as a means to prevent ovarian cancer in average risk premenopausal women.
Bilateral Oophorectomy
is often chosen by many as a method for prevention of ovarian cancer in premenopausal women who are at average risk of ovarian cancer. The procedure
gained popularity in US when Angelina Jolie came forward about her own experiences 2 years
back.She is a carrier of mutation in BRCA1 gene putting her high risk for
ovarian and breast cancer. [1]
The current
guidelines from the American College of Obstetricians and Gynecologists read,
"The most effective method of preventing ovarian cancer is surgical
removal of the ovaries and fallopian tubes. ...The potential benefit in cancer
risk reduction for premenopausal women at average risk of ovarian cancer must
be balanced with the consequences of premature loss of estrogen
production."
However, in
practice many doctors advise patients in favor of removal of both ovaries to
eliminated the risk of getting ovarian
cancer.
Many societies around the world have formulated guidelines so that the surgery is only performed in absolutely indicated patients like BRCA1 positive patients, but the practice still continues.
Observational
studies have also documented the beneficial role of estrogen in keeping chronic
morbidities at bay in women who undergo bilateral oophorectomy
before the age of 46 years.
The present study
was prompted because of uncertainties in the risk/benefit ratio of bilateral oophorectomy
for preventing ovarian cancer and the role played by estrogen in delaying many
chronic morbidities which may be sign of cellular and tissue aging.
The study
was published in the recent issue of Mayo Clinic Proceedings.[2]
The
researchers used the Rochester Epidemiology Project records-linkage system to recruit
1653 women who underwent bilateral oophorectomy before the age of 50 years
between 1988-2007 in Olmsted County, Minnesota. Each subject was than randomly
matched to a control, who was also born in the same year (±1 year), but did not
have bilateral oophorectomy. They were followed up for approximately 14 years
to study 18 comorbidities.
At baseline
it was observed that women who underwent bilateral oophorectomy were Caucasians,
less educated, had increased BMI and were heavy smokers as compared to referral
women. They were also more likely to suffer from mental, Cardiometabolic and
somatic disorders at the time of surgery.
Researchers
used inverse probability weighting to balance the baseline risk factors
and individual characteristics thereby minimizing their effects as potential confounders.
Women who had
bilateral oophorectomy before menopause experienced increased risk of depression,
hyperlipidemia, cardiac arrhythmias, coronary artery disease, arthritis,
asthma, chronic obstructive pulmonary disease, and osteoporosis. (hazard
ratio, 1.22; 95% CI, 1.14-1.31; P<.001).
The younger
the age at oophorectomy, the stronger the association with these chronic
conditions.
In these
group of women, the risk of occurrence of many chronic condition was reduced by
supplementing estrogen therapy.
The
researchers proposed three possible mechanisms to explain the results of the
study. Although inverse probability weighting was used to rule out
confounding and bring the observational study close to RCT for interpretation as
possible, genetic, environmental and lifestyle factors may have acted as
confounders.
Premature
and abrupt decline in estrogen levels may have led to increase in ‘epigenetic
age’ serving as a bio-marker for accelerated aging.
Oophorectomy
leads to loss of protective effect of other ovarian hormones progesterone,
testosterone, or inhibin and disrupts the hypothalamic-pituitary axis.
The study
had several strengths and limitations. As all the data was extracted
electronically it eliminates the recall bias and non- participation of the
subjects. Study may have underestimated those conditions which do not have any
medical code, as the data was extracted form records. Statistical power was limited for some
associations for the time the women were followed. It may become significant if
they are followed for longer period of time.
To Conclude,
the study results along with results of the earlier studies provides definitive
evidence against use of bilateral oophorectomy as a means to prevent ovarian
cancer in average risk premenopausal women. Study also emphasizes the
protective effect estrogen may exert to delay cellular and tissue level
aging which is manifested as increased risk of multiple morbidities.
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