Genitourinary Symptoms of Menopause (GSM) are chronic, progressive conditions of genital, sexual, and urinary symptoms affecting 50%-90% of postmenopausal women. Although GSM has profound consequences for women’s short and long-term health, and quality of life, less than 25% of women discuss their symptoms with their provider, let alone receive treatment.
Since 2003, the Federal Drug Administration (FDA) has placed a “boxed warning” on all estrogen products, regardless of the dosage and delivery method. By carrying the same warnings as systemic estrogen products, the “boxed warning” for local vaginal estrogen overstates its potential risk, deterring doctors from prescribing and women from using this essential treatment. As practitioners who prescribe local vaginal estrogen, we constantly see our patients refuse to use it after reading the insert.
In 2023, Let’s Talk Menopause spearheaded the formation of The Menopause Advocacy Working Group, composed of top experts in the medical field and menopause care advocates. We sat down to chat with Dr. Rachel Rubin, a long-time expert and advocate, to learn more about the Working Group’s recent meeting with the Federal Drug Administration (FDA).
A: The FDA is responsible for making sure drugs are effective and for mitigating risk. If risks do exist, they want to let the public know. Think about the commercials you see on television with long lists of side effects—there is no medication with absolutely no risk and no side effects. When the FDA is worried about very serious side effects, they place a massive “boxed warning” on the medication. The problem is that this “boxed warning” is on all estrogen products regardless of whether it’s a very large, high-dose, whole-body hormone, whether it’s fake estrogen or real estrogen, or whether it’s a localized form of estrogen therapy that is so small that it does not increase your blood levels of estrogen. This is a problem because different estrogen products do different things and have different risks associated with them.
A comparison I often mention is the difference between buying over-the-counter hydrocortisone cream for a bug bite and needing IV steroids in the intensive care unit. They are both steroids but they are different doses, have different risks, and are used to treat different things.
This is SO important because we’re not talking about a little vaginal dryness here. GSM leads to urinary frequency, urgency, and recurrent urinary tract infections (UTI), which put many people in the hospital every year and account for a huge amount of Medicare spending. Using low dose estrogen products can prevent UTIs, save lives, and massive amounts of money for the government. But they are not being used by doctors or patients because of non-evidence-based fears about the dangers of these products. People are afraid of the risks—risks that are not supported by scientific evidence—and the boxed labeling reinforces these fears.
The box is harming women and lying to patients. There is no evidence that vaginal estrogen causes stroke, blood clots, or probable dementia. Women are dying from UTIs, not going to the movies because they urinate every five minutes, not wearing yoga pants because they have so much pain, and not engaging in intimacy with their partners. All while there are safe and effective treatment options available.
A: We have estrogen receptors throughout our whole body. When you use systemic or whole-body estrogen therapy, whether it’s a pill or through the skin via a patch or a cream, it fills up receptors throughout your body. So it may be used to help with hot flashes, night sweats, or osteoporosis. The vaginal estrogen is such a miniscule amount—it’s like one rain drop compared to a rain storm—it’s typically used twice a week and does NOT increase blood levels of estrogen through the whole body. It does not attach to those receptors, and it does not fix hot flashes, night sweats or osteoporosis. But, it does help the local microbiome, and helps prevent UTIs, lubrication, pain with sex, urinary frequency and urgency. It provides a localized treatment and not a whole body treatment, and is very effective at doing so.
It is safe for nearly all people to use localized estrogen—if you have active breast cancer and take an aromatase inhibitor, you should talk to your oncologist. Whereas for systemic hormone therapy, the risk-benefit profile is more nuanced.
A: We are meeting with the FDA because we want to understand the path forward to removing the boxed labeling that is false and hurting patients. We would love to collaborate with them to find a path to increase patient safety.
A: We had a productive meeting and are working with the FDA to identify next steps, along with talking with industry partners, and—here’s where you come in—we need to create public awareness around this issue!
Board-certified urologist and sexual medicine specialist. One of only a handful of physicians withfellowship training in male and female sexual medicine. Clinician, researcher, and passionateeducator. Education chair for the International Society for the Study of Women’s Sexual Health(ISSWSH), and Associate Editor for Sexual Medicine Reviews. Training from Tufts and Georgetown,and with Dr. Irwin Goldstein in San Diego.
