Woman Discussing Hormone Replacement Therapy with her Doctor

Links Between Unopposed Estrogen and Cancer

Links Between Unopposed Estrogen and Cancer

Taking unopposed estrogen with an intact uterus for a long time has been shown to increase the risk of endometrial cancer significantly. Endometrial hyperplasia, an overgrowth in the lining of the uterus, has been demonstrated in as many as 50% of women taking unopposed estrogen within one year (Martin & Barbieri, 2019b). The risk of endometrial carcinoma for women taking unopposed estrogen is approximately 1 in 100; risk increases with time and continued use and persists even after discontinuation (Martin & Barbieri, 2019b).  Long term use of hormone replacement therapy is also associated with an increased risk of cardiovascular events, including stroke (Martin & Barbieri, 2019a,b). Taking estrogen unopposed means you’re taking it without also taking progesterone in conjunction with it. Using estrogen for the management of menopausal symptoms is appropriate in women with an intact uterus, but progesterone must also be provided (Martin & Barbieri, 2019a,b). 

Is It Considered Medical Malpractice If I get Cancer After Taking Unopposed Estrogens?

Such cases could be considered medical malpractice if there is:

  • A failure to obtain a yearly endometrial biopsy.
  • A failure to refer to a Gynecologist if presented with spotting.
  • Continued prescription of unopposed estrogen for a long time with the presence of abnormal vaginal bleeding.

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A failure to obtain informed consent explaining the risks and benefits of estrogen-only hormone replacement therapy. This informed consent should emphasize the possible long-term side-effects of the treatment such as breast cancer, endometrial cancer, and stroke

Screening for Endometrial Cancer

If a postmenopausal woman experiences bleeding, a doctor can investigate using ultrasound or biopsy to rule out the presence of endometrial cancer. An ultrasound is a useful assessment tool of the endometrial lining in postmenopausal women as clinicians have associated an endometrial thickness of greater than five millimeters with a higher risk for endometrial carcinoma. A physician can also use transvaginal as an additional tool for assessment (Feldman, 2019). While ultrasound is useful, endometrial sampling, or biopsy, is the gold standard to assess endometrial hyperplasia for carcinoma (Feldman, 2019).  

You Should Be Monitored

Some patients can’t tolerate progesterone therapy. In such cases, when a physician has prescribed unopposed estrogen, the patient must be monitored closely with yearly endometrial biopsies. Vaginal bleeding in women receiving hormone therapy may require sampling of the endometrium to rule out hyperplasia.(Ref – 1)

Best Practices for Long Term Use of Hormone Replacement Therapy

Before prescribing estrogen therapy to a post-menopausal woman, a physician must weigh the risks and benefits and inform their patient of these risks and benefits. Patients should receive regular clinical follow up to determine if the treatment is still necessary. The increased risk of endometrial cancer in postmenopausal women taking estrogens supplements depends on both the duration of treatment and the estrogen dose. A doctor should utilize the lowest dose that will control symptoms, and they should discontinue medication soon after prescription. Generally, hormone replacement therapy isn’t continued for more than five years. When prolonged treatment is medically indicated, the patient should be reassessed every six months, and the dosage should be adjusted based upon the patient’s response. If they present with abnormal vaginal bleeding, a physician should use adequate diagnostic measures to rule out endometrial carcinoma.(Ref-2)

What to Do Next If I Suspect Medical Malpractice

           The most natural next step would be to speak with an attorney who worked on similar kinds of cases. At Patton and Patton, we have handled medical malpractice cases involving hormone replacement therapy. We offer case evaluations free of charge. After an initial consultation, we would retrieve your medical records and have them evaluated by medical professionals to see if, from a physician’s perspective, there is a clear violation of the standard of care. Give us a call at 785-370-0001, so we can evaluate the details of your specific case.

Summaries and Additional Information

Ref – 1


The patterns of vaginal bleeding in women receiving estrogen therapy vary with the regimen used.

Unopposed Estrogen

Use of unopposed estrogen in women with an intact uterus is not recommended because of the risk of causing endometrial cancer. However, in rare circumstances, when a patient cannot tolerate any form of progestin therapy, and unopposed estrogen is used, the patient must be monitored closely with yearly endometrial biopsies.

Endometrial Monitoring 

Vaginal bleeding in women receiving hormone therapy may require an evaluation of the endometrium to rule out hyperplasia. The indications for monitoring and the choice of the test are dependent upon the estrogen regimen used.


Role of Androgen Therapy

The known decrease in ovarian androgen production rates and serum androgen concentrations has caused concern that menopause might be associated with a decline in libido. An age-associated reduction in sexual desire has been observed in both men and women. However, it is unclear whether the decrease in libido in women is age or menopause-related, since studies in women have not shown a significant correlation between libido and the serum estradiol or testosterone concentration [54].

Clinical trials of exogenous testosterone replacement suggest modest benefits of testosterone therapy in some postmenopausal women. However, there are potential risks associated with androgen replacement, and the use of testosterone is limited by the lack of approved and commercially available products for women. Until the beneficial effects of androgen replacement are better established, it cannot be routinely recommended to postmenopausal women. (See “Overview of androgen deficiency and therapy in women” and “Sexual dysfunction in women: Management”, section on ‘Androgens’.)

Duration of Therapy

For women who choose estrogen or combined EPT, short-term use is suggested (generally not more than five years or not beyond age 60 years [28]). However, hot flashes persist for an average of 7.4 years, and many women continue to have symptoms for more than ten years. Some women with persistent symptoms choose longer-term therapy. (See ‘Extended use of MHT’ below and “Menopausal hot flashes”, section on ‘Duration’.)

For women who experience recurrent, bothersome hot flashes after stopping estrogen, we initially suggest non-hormonal options before considering resuming estrogen. For those who do not get adequate relief with non-hormonal therapies, we consider extended use of hormone therapy. (See ‘Extended use of MHT’ below.)

Exogenous estrogen or estrogen agonists Unopposed estrogen therapy

Systemic estrogen therapy without an opposing progestin in a woman with a uterus results in a markedly increased risk of endometrial hyperplasia or carcinoma.

Endometrial hyperplasia has been demonstrated in 20 to 50 percent of women after one year of receiving systemic estrogen therapy without a progestin [15-17]. Multiple case-control and prospective studies have shown an increased incidence of endometrial carcinoma, with relative risk ranging from 1.1 to 15 [18-20]. The risk is related to both estrogen dose and duration of use.

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Other Medical References:

Martin, K. & Barbieri, R.  (2019a).  Preparations for menopausal hormone therapy.  UpToDate:  Wolters Kluwer.  (Eds. Snyder, P. & Crowley, W).

Martin, K. & Barbieri, R.  (2020b).  Treatment of menopausal symptoms with hormone therapy. UpToDate:  Wolters Kluwer.  (Eds. Snyder, P. & Crowley, W).

Chen & Berek (2020) Endometrial carcinoma: Epidemiology risk factors, and preventions. UpToDate: Wolters Kluwer. (Eds. Levin, D., Goff, B.)

Martin, K. & Barbieri, R.  (2019b).  Menopausal hormone therapy:  Benefits and risks.  UpToDate:  Wolters Kluwer.  (Eds. Snyder, P. & Crowley, W).

Feldman, S. (2019).  Methods for evaluating the endometrium for malignant or premalignant disease.  UpToDate:  Wolters Kluwer.  (Eds. Levine, D., Goff, B.)

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