Friday, September 30, 2016

Premenopausal Bilateral Oophorectomy accelerates aging and incidence of 18 chronic morbidities.

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.  






[1]http://www.nytimes.com/2015/03/24/opinion/angelina-jolie-pitt-diary-of-a-surgery.html?_r=0
[2] http://www.mayoclinicproceedings.org/article/S0025-6196(16)30447-5/fulltext

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