What Do We Know About Vaginal Estrogen?

What are the risks of vaginal estrogen?
What is vaginal estrogen?
Does recent scientific research point to the safety of vaginal estrogen?
Is vaginal estrogen associated with endometrial cancer?
Can you take vaginal estrogen if you have a history of breast cancer?
What are the side effects associated with vaginal estrogen?
Next steps

Introduction

If you’re going through menopause or well beyond it, you may be experiencing firsthand the effects of lower levels of the hormone estrogen. Vaginal dryness, pain, UTIs, and urgency are all hallmark symptoms of menopause due to low estrogen.

Adding estrogen back to the vulva and vagina can not only bring relief - it can help protect your long-term health and quality of life.

And while a trusted medical provider may have prescribed vaginal estrogen to help treat and prevent your symptoms, you may still have questions about its safety. That’s because what your doctor explained to you might differ from the information you’re reading in the boxed instructions.

In this article, we will dive into the literature, research, and expert opinions on vaginal estrogen so that you can feel informed and educated about your treatment options.

What are the risks of vaginal estrogen?

When you open your box of vaginal estrogen, you’ll read an FDA-warning label that says estrogens can increase your risk of cancer and heart disease¹.

Vaginal estrogen in several FDA-approved formulations, including a cream, insert, and ring.

The FDA has approved several formulations of vaginal estrogen, including cream, insert, and ring. All formulations carry the boxed warning for oral estrogen.

The warning label is based on evidence from a 2002 clinical study of oral estrogen. Importantly, oral estrogen is prescribed in higher doses, while vaginal estrogen is prescribed in lower doses.

Now it’s nearly twenty years later, and more research has been done on vaginal estrogen.

In 2018, two large analyses were published that support the safety of vaginal estrogen. Both analyses concluded there is no evidence that vaginal estrogen increases the risk of cancer and heart disease^2,³.

Given the current science, medical practitioners worry that the FDA warning label on vaginal estrogen unnecessarily frightens women. The Menopause Society, for example, has been lobbying the FDA to change the warning label to enhance safety and emphasize the key information that women need to know about vaginal estrogen.

Taking oral estrogen can increase certain health risks. But vaginal estrogen is not shown to carry these risks.

What is vaginal estrogen?

When considering treatments for vaginal and urinary health in menopause, it’s key to understand that there are two main types of menopause hormone therapy:

Systemic hormones are taken as a pill or applied as a patch.
Local therapy that’s applied to the vagina as a vaginal estrogen cream, vaginal estrogen insert, or vaginal ring.

Systemic hormones are absorbed in the bloodstream and can circulate throughout the entire body - which explains the potential health risks. But vaginal estrogen is applied only to affected areas and generally does not elevate blood estrogen levels beyond what’s considered normal for postmenopausal women^4,⁵.

Vaginal estrogen products approved by the FDA

Brand name	Does data show blood estrogen levels are within normal range?
Estrace vaginal cream	Yes, but sometimes no
Premarin vaginal cream	Yes
Yuvafem or Vagifem vaginal insert	Yes
Estring vaginal ring	Yes

While there are possible health risks associated with systemic hormones, the expert opinion of The Menopause Society is that these risks are unlikely when using vaginal estrogen, since there is minimal absorption in the bloodstream.

View of a woman wearing a bathing suit and surfing.

Vaginal estrogen is applied only to the affected areas of the vagina and vulva and does not raise estrogen hormones beyond normal ranges.

Does recent scientific research point to the safety of vaginal estrogen?

Large amounts of clinical data point toward the safety of vaginal estrogen. For example, two large analyses concluded that vaginal estrogen is not shown to increase risk of cancer or heart disease.

According to a 2018 analysis of data from the WHI Observational Study, there was no difference in health risks between people who used vaginal estrogen and people who did not³. The findings are consistent with a 2018 analysis of clinical data from another large study called The Nurses’ Health Study.

Health risks of people who use vaginal estrogen compared to people who don’t use vaginal estrogen

Risk of stroke	No increased risk
Risk of invasive breast cancer	No increased risk
Risk of colorectal cancer	No increased risk
Risk of endometrial cancer	No increased risk
Risk of pulmonary embolism/deep vein thrombosis	No increased risk
Risk of coronary heart disease	No increased risk
Risk of fracture	No increased risk
Risk of all-cause mortality	No increased risk
Risk of GIE	No increased risk

Based on data from 93,676 women who participated in the Women’s Health Initiative study.

Is vaginal estrogen associated with endometrial cancer?

Clinical data shows that vaginal estrogen is not associated with endometrial cancer. But the endometrial safety is not studied in clinical trials beyond one year.

The Menopause Society states that while there is reassuring evidence that vaginal estrogen is not associated with an increased risk of endometrial cancer, more research is needed regarding long-term use.⁴

Regardless of whether you are taking vaginal estrogen, endometrial cancer is rare. But here are some general guidelines:

You don’t need to be monitored for endometrial cancer if you are using vaginal estrogen.
Take note of any vaginal bleeding. Vaginal bleeding outside of your menstrual cycle could indicate a serious condition.
If you experience vaginal bleeding, it should be assessed by a primary care physician or gynecologist.

The endometrial safety of vaginal estrogen has not been studied in clinical trials longer than 1 year, although observational studies are reassuring regarding longer-term use.

Can you take vaginal estrogen after breast cancer?

According to a 2021 expert opinion from the American College of Gynecologists published in 2021, women with a history of breast cancer may consider using vaginal estrogen at the lowest effective dose if non-hormonal treatments are not adequate to address symptoms.

However, if you wish to try vaginal estrogen, clear it with your oncologist first. Before your appointment, you should prepare to communicate your values, preferences, and symptom severity and then seek to understand the potential risks in your unique case.

Woman squeezing vaginal cream out of a tube.

If vaginal moisturizers and lubricants have little effect, women with a history of breast cancer can take vaginal estrogen if they have approval from their oncologist.

What are the side effects associated with vaginal estrogen?

Side effects associated with the use of vaginal estrogen include vaginal discharge, yeast infection, vaginal bleeding, and breast pain. If you’re experiencing unintended side effects, or if there’s something else, talk to a trusted medical provider. Some side effects may be caused by variations in formulation or dosage. Your provider may be able to help make adjustments.

Next steps

While the latest scientific research points to the safety of vaginal estrogen, the information on the product label can understandably cause confusion or fear. Therefore, discussing your symptoms and goals with a trusted medical provider is key.

When it comes to treating vaginal and urinary symptoms from menopause, you have options.

Moisturizers and lubricants. As an initial solution, you might try vaginal moisturizers or lubricants like coconut oil. These treatments are available over the counter, and can relieve dryness, itching, and discomfort.
Vaginal estrogen. If you’re not getting relief from moisturizers and lubricants, then it may be time to consider vaginal estrogen. Vaginal estrogen can help reverse vaginal atrophy, restore vaginal moisture, and prevent UTIs. Vaginal estrogen can also help keep the vaginal pH at healthy levels. While vaginal estrogen is available over the counter in countries like the UK, it’s available only as a prescription in the United States.
Other options. In addition to vaginal estrogen, the FDA has also approved vaginal DHEA, systemic estrogen therapy, and Ospemifene for the treatment of vaginal and urinary symptoms.

Vaginal and urinary symptoms do not get better with time. By taking action now, you can prevent issues like urgency, dryness, and UTIs from worsening. At Interlude, we want you to feel safe and educated about your treatment options. Sexual health is such an important and private topic. We’re making it more approachable so that more women can live pain-free.

Disclaimer: This information isn't a substitute for professional medical advice, diagnosis, or treatment. You should never rely upon this article for specific medical advice. If you have any questions or concerns, please talk to your doctor.

References

1 ESTRACE package insert

2 Bhupathiraju S, Grodstein F, Stampfer M, et al. Vaginal estrogen use and chronic disease risk in the Nurses’ Health Study. Menopause. 2018;26(6):603-610.

3 Crandall CC, Hovey K, Andrews C, et al. Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women’s Health Initiative Observational Study. Menopause. 2018;25(1):11-20.

4 North American Menopause Society. The 2020 genitourinary syndrome of menopause position statement of The North American Menopause Society. Menopause. 2020;27(9):976-992. Health Qual Life Outcomes. 2005;3:47.

5 Pinkerton J, Liu J, Santoro N, et al. Workshop on normal reference ranges for estradiol in postmenopausal women: commentary from the North American Menopause Society on low-dose vaginal estrogen labeling. Menopause. 2020;27(6):611-613.