APPENDIX VIII: PROPHYLACTIC OOPHORECTOMY

Carolyn D. Runowicz, MD

In hereditary forms of ovarian cancer, onset usually occurs between ages 35 and 45. Based on this information, women over 35 years of age could be offered prophylactic oophorectomy as an option. However, the optimum age has not been established.

Prophylactic surgery, involving bilateral salpingo-oophorectomy, is a viable consideration in carefully selected patients at unequivocally high genetic risk for ovarian cancer. However, many issues remain unresolved:

1. physiologic adjustments to a premature surgical menopause, especially vasomotor symptoms - prevention of cardiovascular disease and osteoporosis are critical issues

2. psychosocial adjustments to premature menopause

3. hormone replacement therapy, especially in those women with a high risk of breast cancer - data also suggest that there is poor compliance with long-term hormonal therapy

If a patient at risk for ovarian cancer is having abdominal/pelvic surgery, a prophylactic oophorectomy should be performed. It has been reported that elective routine removal of ovaries after age 40 would eliminate approximately 12-14% of all ovarian cancers.¹ The added surgical morbidity of oophorectomy at the time of laparotomy/laparoscopy for other indications is minimal. The physiologic and psychosocial issues associated with premature menopause and hormone replacement therapy need to be addressed.

Patients considered for prophylactic surgery should have completed their desired childbearing. They should receive genetic counseling and must understand that the surgery will produce a premature menopause and irreversible infertility, when combined with a total hysterectomy. They need to be informed about hormone replacement therapy and the issue of noncompliance with long-term medication should be addressed. The risk of osteoporosis and heart disease need to be considered in pre-surgical counseling.

The efficacy of prophylactic oophorectomy in individuals with strong family histories of breast/ovarian cancer has been evaluated in observational studies. The failure rate ranges from 2%-11%.^1,2,3,4 These results suggest that there is some protective effect.

Recommendations from other agencies or groups:

American College of Obstetricians and Gynecologists (1992)

• Women with familial ovarian or hereditary breast/ovarian cancer syndromes who do not wish to maintain their reproductive capacity may be offered prophylactic bilateral salpingo-oophorectomy. Such women should have a documented familial syndrome, preferably established via a full pedigree analysis by a geneticist. These women should be informed that removal of the tubes and ovaries does not provide 100% protection; primary peritoneal carcinoma has been reported after bilateral salpingo-oophorectomy in some cases.

National Institute of Health Consensus Statement on Ovarian Cancer (1994)⁵

• The probability of a hereditary ovarian cancer syndrome in a family pedigree increases with the number of affected relatives, with the number of affected generations, and with young age of onset of disease. Therefore, prophylactic oophorectomy should be considered in these settings with careful weighing of the risks and potential benefits. The risk of ovarian cancer in women from families with hereditary ovarian cancer syndromes is sufficiently high to recommend prophylactic oophorectomy in these women at age 35 or after childbearing is completed.

Prevention:

Clearly established protective factors include greater than one full-term pregnancy, oral contraceptive use, and breast-feeding, all of which reduce incessant ovulation. Tubal ligation has also been described as a possible protective factor.⁶ The risk reduction associated with greater than five years of oral contraceptive use is estimated in one study to be 37%.⁷ Relatively short duration of use may be beneficial, but prolonged use appears to extend this benefit.

References:

1. Nguyen HN, Averette HE, Janicek M. Ovarian carcinoma: a review of the significance of familial risk factors and the role of prophylactic oophorectomy in cancer prevention. Cancer 1994;74:545.

2. Kerlikowske K, Brown JS, Grady DG. Should women with familial ovarian cancer undergo prophylactic oophorectomy? Obstet Gynecol 1992;80:700.

3. Struewing JP, et al: Prophylactic oophorectomy in inherited breast/ovarian families. JNCI Monographs 1995;17:33.

4. Piver MS, Jishi MF, Tsukasla Y, Nava G. Primary peritoneal carcinoma after prophylactic oophorectomy in women with a family history of ovarian cancer: a report of the Gilda Radner Familial Ovarian Cancer Registry. Cancer 1993;71:2651.

5. NIH Consensus Development Panel on Ovarian Cancer. Ovarian cancer screening, treatment and follow-up. JAMA 1995; 273:491.

6. Hankinson SE, Hunter DJ, Colditz GA et al. Tubal ligation, hysterectomy, and risk of ovarian cancer: a prospective study. JAMA. 1993; 270: 2813-2818.

7. Grimes, DA. The safety of oral contraceptives: epidemiological insights from the first thirty years. Am J Obstet Gynecol. 1992; 166: 1950-1954.