Unopposed estrogen hormone replacement therapy (HRT) involves taking estrogen without an opposing progestogen. Estrogen is commonly prescribed to treat menopausal symptoms like hot flashes, vaginal dryness, and sleep disturbances. It can be given orally, transdermally, or locally as a vaginal cream or tablet.
The main concern with unopposed estrogen therapy is an increased risk of endometrial hyperplasia and endometrial cancer. The estrogen causes proliferation of the endometrial lining, which can become abnormal over time if not balanced by progesterone. This is why unopposed estrogen is generally avoided in women with an intact uterus.
Some of the estrogen-only regimens used include:
- Oral estradiol - Transdermal estradiol patch - Vaginal estrogen cream or tablet
These deliver estrogen without any opposing progestogen. Progestogens like progesterone, medroxyprogesterone acetate, and norethindrone acetate oppose the effects of estrogen on the endometrium and reduce cancer risk. That's why combined estrogen-progestogen therapy is preferred for women with a uterus.
However, unopposed estrogen may be used selectively in certain cases, such as:
- Women without a uterus: Unopposed estrogen is safe in women after hysterectomy since there is no endometrial tissue at risk. This includes transgender women as well.
- Short-term use: Some providers may prescribe short course unopposed estrogen for severe menopausal symptoms if the benefits are felt to outweigh the low risk. This is very selective use for just a few months.
- Certain uterine conditions: Unopposed estrogen may be used in women with thin endometrium like in Asherman syndrome. The estrogen works to stimulate endometrial growth in this case.
- Women opposed to progesterone: Some women experience side effects like mood changes, headaches, or fluid retention on progestogens. Unopposed estrogen may be considered for those unwilling to take progesterone. However, they require vigilant monitoring.
If unopposed estrogen is used, regular monitoring is critical to check for endometrial thickening or abnormality. This includes:
- Transvaginal ultrasound: Periodic ultrasound is done to measure endometrial stripe and assess for any abnormal thickening or pathology. This is the mainstay of monitoring on unopposed estrogen.
- Endometrial biopsy: A small sample of the endometrial tissue may be taken to check for precancerous changes. This is considered if ultrasound shows significant thickening.
- Dilatation & curettage (D&C): In some cases of endometrial hypertrophy, a D&C may be done to remove excess tissue and provide material to test for abnormal cells.
Unopposed estrogen increases endometrial cancer risk in a dose and duration-dependent manner. The risk is estimated to be 2-10 times higher compared to combined estrogen-progestogen therapy. Lower-dose vaginal estrogen may carry a lower risk than oral formulations.
To mitigate the risks of unopposed estrogen:
- Use the lowest effective estrogen dose to manage symptoms - Limit duration to 3-6 months if possible - Monitor with regular ultrasound and possible biopsy - Be vigilant about abnormal uterine bleeding which requires urgent evaluation
Of course, the safest approach is to add a progestogen to counteract the estrogenic effect on the endometrium. For most women with a uterus, combined HRT with both estrogen and progesterone is the standard. But unopposed estrogen has selective applications in managing menopause in some situations as described. With careful patient selection and close surveillance, it may be used judiciously in certain cases. The goal is balancing benefits against endometrial cancer risks.
At Balance Hormone Center, our physicians have extensive experience in hormone therapy including unopposed and combined regimens. We take a personalized approach focused on safety while optimizing symptom relief. Contact us for an evaluation of your menopause and hormone replacement options. We'll listen to your concerns and goals, perform needed exams, review your risks, and develop an individualized treatment plan just for you. You'll also have close follow-up to ensure your therapy stays on track. Reach out today to start your hormone balancing journey.
