From the Guidelines
Hyperplasia without atypia occurs from unopposed estrogen because estrogen stimulates the growth and proliferation of endometrial cells without the counterbalancing effects of progesterone. This condition is a result of the continuous promotion of cell division and tissue growth by estrogen, leading to an abnormal thickening of the endometrial lining, as seen in studies where unopposed estrogen use was associated with an increased risk of endometrial cancer, with a relative risk of 2.3 (95% CI, 2.1 to 2.5) compared to nonusers 1. The risks increased with increasing duration of use, with a relative risk of 9.5 for 10 years of use, and the risk remained elevated 5 or more years after discontinuation of unopposed estrogen therapy 1.
Key Points
- Unopposed estrogen stimulates endometrial cell growth and proliferation
- Progesterone normally opposes estrogen's action by promoting cell differentiation and maturation
- Common scenarios causing unopposed estrogen include anovulatory cycles, polycystic ovary syndrome, obesity, estrogen-secreting tumors, and exogenous estrogen therapy without progesterone
- Treatment typically involves progesterone therapy to counteract estrogen's effects, such as oral progestins or a levonorgestrel-releasing intrauterine device
Clinical Implications
The use of unopposed estrogen is associated with an increased risk of endometrial cancer, and the risk remains elevated even after discontinuation of therapy 1. Therefore, it is essential to use combined estrogen-progestin regimens to minimize the risk of endometrial cancer. In cases where hyperplasia without atypia occurs, treatment with progesterone therapy can help restore normal endometrial architecture and reduce the risk of progression to endometrial cancer.
From the Research
Hyperplasia without Atypia and Unopposed Estrogen
- Hyperplasia without atypia occurs due to unopposed estrogen, which can be caused by various factors such as hormone replacement therapy, tamoxifen, or conditions that increase levels of circulating estrogen like obesity or estrogen replacement therapy 2, 3, 4.
- Unopposed estrogen stimulates the growth of the endometrium, leading to hyperplasia, which can progress to endometrial cancer if left untreated 2, 5, 3, 4.
- The risk of hyperplasia without atypia is increased in women with conditions associated with intermittent or absent ovulation, such as polycystic ovary syndrome, and in postmenopausal women with unopposed estrogen 2, 3, 4.
Treatment and Management
- Hyperplasia without atypia responds well to progestins, which can help to reduce the risk of progression to endometrial cancer 2, 5, 4.
- The choice of treatment for hyperplasia without atypia depends on patient age, the presence of cytologic atypia, the desire for future childbearing, and surgical risk 2, 5, 4.
- Progestin therapy has been shown to decrease the risk of endometrial carcinoma and hysterectomy in women with complex and atypical hyperplasia 5.
Diagnostic and Predictive Factors
- The expression of estrogen and progesterone receptors (ER and PR) may predict the response to conservative treatment of endometrial hyperplasia and cancer, but their accuracy is insufficient to be determining in clinical practice 6.
- Negative PR expression has been shown to predict poor response to progestin therapy, while negative ER expression does not significantly predict poor response 6.