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Am Fam Physician. 2000;61(4):1155-1156

Estrogen replacement therapy is usually not prescribed to patients who have undergone hysterectomy and oophorectomy for ovarian cancer, although data are lacking on whether exogenous estrogen increases the chance of relapse. To address this issue, Guidozzi and Daponte performed a randomized controlled trial of estrogen replacement therapy in women with ovarian carcinoma.

The study included 130 women from 27 to 59 years of age with a history of invasive epithelial ovarian carcinoma. Eighty-four of the patients had stage III ovarian cancer, 16 had stage I cancer, 13 had stage II and 12 had stage IV. Final analysis included 59 patients who received 0.625 mg of conjugated oral estrogen daily and 66 patients who did not. Patients who had previously received conjugated estrogens or who had cancer with low malignant potential were excluded from the study. Surgical treatment of ovarian cancer included tumor debulking, total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy. Patients also received six cycles of cisplatin and cyclophosphamide therapy and then two cycles of cisplatin only. Chlorambucil was administered for one year thereafter.

Follow-up visits occurred every three to six months, with ultrasonography and/or computed tomography performed every six months or when these studies were clinically indicated. Carcinoembryonic antigen 125 was determined monthly for the first year and every three months thereafter. Follow-up was a minimum of 48 months.

The rate of cancer recurrence did not differ significantly in the two groups. Cancer recurred in 32 (54 percent) of the patients who received hormone replacement, compared with 41 (62 percent) of the patients who did not receive hormone replacement. Recurrence was most common in women with poorly differentiated tumors and stage III or stage IV disease. Patients who had recurrence of cancer were treated with additional cycles of chemotherapy, and approximately one third of each group had a second surgery.

The median disease-free interval was 34 months in patients who received estrogen and 27 months in those who did not. The median duration for overall survival was 44 months in the hormone replacement group and 34 months in the group who did not receive estrogen.

When data on patients with stage III disease were analyzed, the median disease-free survival was 25 months for the hormone replacement group and 23 months for the group who did not receive hormone replacement. The median duration of survival for patients with stage III cancer was 32 months in those who received estrogen and 29 months in those who did not. None of these differences was statistically significant.

The authors conclude that estrogen replacement therapy does not adversely affect the disease-free interval or overall survival in women with ovarian cancer. In addition, the authors note that estrogen replacement may improve quality of life in women who experience premature menopause secondary to oophorectomy.

editor's note: Even though the number of patients in this study was small, the authors state that for the past two years they have offered estrogen replacement therapy to all of their patients with ovarian cancer. In long-term survivors of ovarian cancer, the additional benefits of protection from osteoporosis and heart disease (beyond relieving the symptoms of menopause) should be considered. Hopefully, other prospective trials will yield results similar to the findings of this study.—j.t.k.

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