Progestin for Atypical Hyperplasia and Endometrial Carcinoma in Women Under Age 40

Abstract & Commentary

Synopsis: Treatment of atypical hyperplasia and well-differentiated carcinoma of the endometrium with progestins appears to be a safe alternative to hysterectomy in women younger than age 40.

Source: Randall TC, Kurman RJ. Obstet Gynecol 1997;90:434-440.

Randall and kurman conducted a retrospective review of the Johns Hopkins experience to determine the efficacy of conservative management of atypical hyperplasia and well-differentiated carcinoma of the endometrium in women younger than age 40. Medical records of such patients seen between January 1990 and January 1996 were identified and reviewed. All available biopsy, curettage, and hysterectomy specimens were reviewed. Follow-up was obtained from the patients’ gynecologists. Sixty-seven records were identified. Atypical hyperplasia was found in 32 patients and well-differentiated carcinoma in 35 patients. Seven patients were excluded from analysis; four declined all treatment and follow-up, and three received no further treatment or tissue sampling from their physicians.

Among 27 evaluable patients with atypical hyperplasia, eight underwent hysterectomy, two were treated with ovulation induction, and 17 were treated with progestins, of which 16 had regression of their lesions and one a persistent lesion. Among 33 women with well-differentiated carcinoma, 19 underwent hysterectomy, one was treated with bromocriptine, one was treated with oral contraceptives, and 12 were treated with progestins, of whom nine had regression of their lesions and three had persistent lesions. The median length of treatment required for regression was nine months. At a mean follow-up of 40 months, all patients were alive and well without evidence of progressive disease. Twenty-five women attempted to become pregnant, and five delivered healthy, full-term infants. Randall and Kurman conclude that treatment of atypical hyperplasia and well-differentiated carcinoma of the endometrium with progestins appears to be a safe alternative to hysterectomy in women younger than age 40.

COMMENT BY DAVID M. GERSHENSON, MD

The findings of this study are indeed provocative but must be viewed with some caution. During my career, I have been a strong advocate of conservative treatment for young women with precancerous lesions or cancer in an effort to preserve fertility when appropriate. Such strategies, however, must be balanced with safety consideration based on available scientific evidence. The results presented here are very encouraging, and the details are important. First of all, the numbers are still small, and the mean follow-up time for the study population is less than four years. Progestational therapy has been used as an alternative to hysterectomy in young patients for several years. Of 17 patients treated with progestins, 16 had regression, and one had persistence; of two patients treated with ovulation induction, one had regression, and one developed progressive disease with well-differentiated carcinoma. Two of these patients had relatively full-term pregnancies with healthy infants. For young patients with well-differentiated carcinoma, conservative treatment with progestins is less well-accepted. Of 12 patients treated with progestins, nine (75%) had regression, and three had persistence. In addition, two of the women with persistent carcinoma were found to have coexistent primary stage I endometrioid carcinomas of the ovary at surgery. Three of the women with well-differentiated carcinoma had five full-term pregnancies with healthy infants. In approaching patients such as these, several factors must be considered. What should be the "gold-standard" procedure for a baseline prior to initiating progestin therapy? Endometrial biopsy, D&C, or hysteroscopy and D&C? These young women and their families need to be carefully counseled about the risks of such a conservative approach, namely progression of disease with metastasis and possible death, as well as the possibility of coexistent endometrioid carcinoma of the ovary. Based on these findings, the probability of such must be small. But how small? How often should the patient on progestin therapy have her endometrium sampled—every three months or every six months? And, for how long should this interval be maintained? And, when is it safe to attempt pregnancy? Clearly, more experience is required before many of these questions can be answered. In the meantime, however, a conservative approach in young women should be considered as long as informed consent is provided and there is adequate documentation in the medical record. Randall and Kurman do point out the fact that young women with endometrial cancer do appear to have a better outcome than older women.