18 August, 2014

Ovarian conservation at the time of hysterectomy for benign disease has certainly become more common, mainly as the result of the landmark paper of Parker and colleagues [1]. This was a focal point in the beginning of a turnaround in the thinking of many clinicians. Now a new body of work examining a portion of this argument comes from the Cancer Prevention Study-II Nutrition Cohort published in Obstetrics & Gynecology by Gaudet and colleagues [2].

It was a fairly straightforward cohort study involving over 66,000 postmenopausal women. In a median follow-up of just under 14 years, 8621 cancers were diagnosed (12.9% of the cohort). The authors compared hysterectomy with BSO at any age (1892 cases) with no hysterectomy (5586 cases) and found a statistically significant 10% reduction in all cancers. However, if the surgery was performed at age 55 or older, there was no reduction in overall cancer, yet hysterectomy with BSO at any age resulted in a 20% reduction in breast cancer that was statistically significant.

Finally, hysterectomy without BSO if performed in women at age 45 or younger, was associated with a 12% decrease in all cancer, and, at any age, with a 14% decrease in breast cancer, both of which were statistically significant. The authors concluded that this information should be used in counseling women undergoing hysterectomy.

Comment

A rallying cry for many of us with an interest in menopausal medicine has been and still is 'one size does not fit all'. When I was a student another rallying cry was 'no end organ, no end organ disease'. Virtually all women in the US over 45 and many over age 40 had routine BSO at the time of hysterectomy for benign disease. Certainly, the understanding of BRCA 1 and BRCA 2, as well as the existence of primary peritoneal carcinoma, underscores that that thought process is not always the case, although it is a minority of patients. Still, the wisdom and the data indicate that BSO will reduce subsequent ovarian cancer. However, hysterectomy, even with ovarian conservation, itself appears to reduce the risk of ovarian cancer by 10–40% – probably because abnormal appearing ovaries are usually removed at hysterectomy [3,4] as well as the fact that almost one-third of women experience menopause within 2 years after hysterectomy, even with ovarian conservation [5].

What about Gaudet's epidemiologic findings about breast cancer? It is well known and not surprising that removing estrogen from premenopausal ovaries will be expected to and does reduce breast cancer risk. These findings of this reduction at any age and even without BSO deserve at least some hypothesis. Ovarian life is certainly diminished by hysterectomy, presumably due to a decrease in blood supply and, as mentioned above, one-third of such women are menopausal within 2 years.

In addition, postmenopausal ovaries continue to make androgens, which are converted into circulating estrogen, so a reduction in breast cancer, even when postmenopausal ovaries are removed, is not surprising.

Still, all of this must be balanced between the benefits of retaining ovaries, and this was the basis of this model first proposed by Parker [1]. In such a model, ovarian conservation reduced enough heart disease and hip fracture cases to more than offset new cases of ovarian and breast cancer. About half of all women older than 40 will die of heart disease [6] while less than 4% die of breast cancer and less than 1% die of ovarian cancer [7]. So, if women undergoing hysterectomy for benign disease are roughly 50 times more likely to die from heart disease than ovarian cancer and 12 times more likely than breast cancer, then even a small protective effect of ovarian conservation on heart disease will outweigh the potential for ovarian or breast malignancies.

However, in my opinion, we still finish where we started ... 'one size does not fit all'. Each patient should be counseled and evaluated individually. A thorough discussion with each patient that takes in account her individual risk profile, but also the psychological weight she attaches to the various outcomes, is essential.
Steven R. Goldstein, MD
Professor of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA

References

1. Parker WH, Broder MS, Liu Z, Shoupe D, Farquhar C, Berek JS. Ovarian conservation at the time of hysterectomy for benign disease. Obstet Gynecol 2005;106:219-26
http://www.ncbi.nlm.nih.gov/pubmed/19384117

2. Gaudet MM, Gapstur SM, Sun J, Teras LR, Campbell PT, Patel AV. Oophorectomy and hysterectomy and cancer incidence in the Cancer Prevention Study-II Nutrition Cohort. Obstet Gynecol 2014;123:1247-55
http://www.ncbi.nlm.nih.gov/pubmed/24807324

3. Parazzini F, Negri E, La Vecchia C, Luchini L, Mezzopane R. Hysterectomy, oophorectomy, and subsequent ovarian cancer risk. Obstet Gynecol 1993;81:363-6
http://www.ncbi.nlm.nih.gov/pubmed/8437787

4. Chiaffarino F, Parazzini F, Decarli A, et al. Hysterectomy with or without unilateral oophorectomy and risk of ovarian cancer. Gynecol Oncol 2005;97:318-22
http://www.ncbi.nlm.nih.gov/pubmed/15863124

5. Siddle N, Sarrel P, Whitehead M. The effect of hysterectomy on the age at ovarian failure: identification of a subgroup of women with premature loss of ovarian function and literature review. Fertil Steril 1987;47:94-100
http://www.ncbi.nlm.nih.gov/pubmed/3539646

6. National Cancer Institute, Statistical Research and Applications Branch. DevCan database: SEER 13 incidence and mortality, 2000-2002, release April 2005, based on the November 2004 submission. For more information see:
http://www.srab.cancer.gov/devcan/ (link expired)

7. American Heart Association. Heart disease and stroke statistics – 2005 update. Available at:
http://www.americanheart.org./presenter.jhtml?identifier+1200026