Hormone Replacement Therapy Formulations and Risk of Epithelial Ovarian Cancer

Abstract & Commentary

Synopsis: This study did not suggest any consistent pattern of altered risk for ovarian cancer and the overall use of HRT by specific formulations of HRT

Source: Sit A, et al. Gynecol Oncol. 2002;86:118-123.

Sit and Associates from the University of Pittsburgh assessed the association between the use of Hormone Replacement Therapy (HRT) and the risk of invasive epithelial ovarian cancer in women participating in a population-based, case-control study conducted in the Delaware Valley from 1994 to 1998. Cases aged 45 or older at diagnosis (n = 484) were compared to community controls (n = 926) frequency matched by age and area of residence. Information on HRT formulation, timing, and duration were obtained by in-person interviews conducted by trained interviewers. HRT formulations were classified as opposed (estrogen + progestin) or unopposed (estrogen alone). They were further categorized according to the estrogen component as either conjugated equine estrogen (CEE), the most common formulation, or non-CEE. Overall, no association was found between any use of HRT and epithelial ovarian cancer. Although use of unopposed non-CEE was associated with a significant decrease in risk among hysterectomized women (OR = 0.17), this was not true for women with intact uterus (OR = 1.14). No significant differences in ovarian cancer risk were observed for other HRT formulations. Sit et al concluded that their results did not suggest any consistent pattern of altered risk for ovarian cancer and the overall use of HRT by specific formulations of HRT.

Comment by David M. Gershenson, MD

The recent findings of several epidemiologic studies of the benefits and risks of HRT have understandably concerned the public and have challenged the dogma like never before. As obstetrician-gynecologists, we are as perplexed as the public by the conflicting results arising from these very complex epidemiologic investigations. While much of the recent media attention has focused on the influence of HRT on breast tissue, bones, and the cardiovascular system, a number of studies, like this one by Sit et al, have addressed the risk of ovarian cancer. The findings regarding the association between HRT and risk of ovarian cancer have been very conflicting. In a thorough review of the subject in an editorial accompanying this article authored by Dr. Harvey Risch, possible explanations for this disparity in the findings are discussed.1 As Dr. Risch points out, variables within these studies include the type of HRT formulation, the duration of use, the latency period, and age during usage. He suggests that, if there is an increased risk of ovarian cancer associated with HRT, the magnitude of risk increase is most probably small. In yet another recent study published in the Journal of the American Medical Association, Lacey and colleagues found that women who used estrogen-only HRT were at significantly increased risk of ovarian cancer.2 This was true particularly for those women who used the medication for 10 or more years. Interestingly, those women in this study who used short-term estrogen-progestin-only replacement therapy were not at increased risk. Until more definitive information is forthcoming, it will be left to each physician and woman to arrive at their best personal decision regarding HRT. But, in my view, the influence of HRT on ovarian cancer risk should take a backseat to other considerations—osteoporosis, breast cancer risk, cardiovascular disease, vasomotor symptoms, vaginal symptoms, the uterine cancer risk—in this decision-making process.

Dr. Gershenson is Professor and Chairman, Department of Gynecology, M.D. Anderson Cancer Center, Houston, Tex.


1. Risch HA. Gynecol Oncol. 2002;86:115-117.

2. Lacey JV, et al. JAMA. 2002;288:334-341.