2011 SABCS, San Antonio Breast Cancer Symposium, 6-10 December, San Antonio, USA

Long term effects oophorectomy, at a young age, on bone health

Dr Anne Marie McCarthy – Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

Let’s start with some background: what is oophorectomy? Oophorectomy is the surgical removal of the ovaries; bilateral oophorectomy, which is the focus of our study, means that both ovaries are removed. There are approximately 300,000 oophorectomies performed each year in the United States and that’s based on data up until 2004. In premenopausal women oophorectomy results in abrupt menopause which causes dramatic reductions in oestrogen and can affect bone health. Hysterectomy is the surgical removal of the uterus and often oophorectomy and hysterectomy are performed at the same time.

The motivation for our study was to examine the long-term effects of oophorectomy at a young age on bone health so that we can inform women at high risk for ovarian and breast cancers and others in whom oophorectomy is recommended and implement appropriate monitoring and preventive strategies.

As I just mentioned, women at high risk for breast and ovarian cancers, such as BRCA1 and 2 mutation carriers, are recommended to have their ovaries removed at a young age. However, this is a small segment of the population and there are other reasons why women have their ovaries removed. The second reason why women may have an oophorectomy is for non-cancer medical indications such as ovarian cysts. In addition, oophorectomy is often performed in women having a hysterectomy for benign medical conditions; some conditions that may warrant a hysterectomy are fibroids, abnormal bleeding, pelvic infection, endometriosis, uterine prolapse and pelvic pain. Often in these cases the ovaries are removed to prevent ovarian cancer and this is the most common reason for oophorectomy, approximately half of all hysterectomies include an oophorectomy.

So what do we know about menopause and bone health? We know that premature natural menopause increases the risk of osteoporosis; also low bone mineral density is associated with an increased risk of fracture and osteoporosis. DEXA scans, which are a special form of X-ray, are a good measure of bone mineral density. In a few studies after even a few years women who underwent an oophorectomy at a young age appeared to have significant bone loss. So for our study we used data from the Third National Health and Nutrition Examination Survey, or NHANES 3 for short. NHANES 3 was a CDC conducted study, it was conducted from 1988 to 1994 to assess the health and nutritional status of the US population. NHANES 3 is a large, nationally representative sample that included detailed health interviews and examinations so when women came in for their health interview they were asked, “Have you had your ovaries removed? Have you had your uterus removed? At what age did you have those surgeries?” In addition, DEXA scans of the femoral neck, which is in the hip, were done on a majority of women.

When we compared bone mineral density in women with oophorectomy and in women with intact ovaries we found that women who had an oophorectomy before age 45 had lower average bone mineral density. Furthermore, among women who never used hormone replacement therapy, which can counteract the effect of lost ovarian hormones, women who had an oophorectomy before age 45 were more than twice as likely to have very low bone mineral density. We also observed that women with oophorectomy before age 45 were nearly twice as likely to report being diagnosed with arthritis.

The implication of our findings are that women who have had their ovaries removed at a young age can now be informed about their risk for bone loss over the long-term. However, additional studies are needed to determine the frequency of monitoring for osteoporosis and the appropriateness of various preventive strategies in women who have their ovaries removed. We are currently conducting a study measuring bone mineral density before and after oophorectomy in women at high risk of breast and ovarian cancers. With respect to arthritis, further studies are required to confirm our findings and to evaluate the underlying mechanisms. To our knowledge, oophorectomy has not been linked to arthritis in clinical studies, there is some data supporting the link in animal studies.

In conclusion I’d just like to acknowledge the participants of NHANES 3 as well as the Breast Cancer Research Foundation which supported this work.