Can you take progesterone without estrogen?

Estrogen gets most of the glory when it comes to hormone replacement therapy (HRT), sometimes called menopause hormone therapy (MHT). And this is for a good reason: That’s the hormone that does the heavy lifting with improving menopause symptoms like hot flashes, as well as preventing bone and muscle loss. But for most women taking HRT, estrogen doesn’t act alone — it’s often paired with another hormone, progesterone, to prevent the uterine lining from growing too thick (something that increases uterine cancer risk).

But estrogen and progesterone don’t always go hand-in-hand. Women without a uterus due to a hysterectomy can take estrogen alone, says Dr. Paru David, M.D., an internist focused on women’s health at Mayo Clinic Arizona, as can women with certain IUDs. But is the opposite true? Can you ever take progesterone without estrogen for menopause? It turns out there are some cases when it might make sense, David says. Keep reading for more about these two hormones and how they work together — and separately.

Is it safe to take progesterone without estrogen?

Taking estrogen alone has risks for most women, as it can cause the lining of the uterus to grow unchecked — raising the risk for uterine cancer. But on the flip side: “There is nothing inherently unsafe in taking progesterone alone,” says Dr. Nanette Santoro, M.D., a professor and E Stewart Taylor Chair of Obstetrics & Gynecology at the University of Colorado School of Medicine. But there are a few risks to be aware of:

• Breakthrough bleeding: “Progesterone mainly has its effects on the lining of the uterus,” David says. “So if some women take the progesterone without estrogen, there is this possibility that it can cause that lining of the uterus to become very fragile and it will tend to want to bleed.”

• Fatigue: “Progesterone is active in the central nervous system,” Santor says. “At very high doses, it's actually an anesthetic.” At low doses, she says, some women say the sedating effect helps them sleep and improves anxiety, but for others, it causes them to be groggy during the day.

• Stroke: Depo-Provera, a birth control shot that has the hormone progestin, can increase the risk of stroke in some women. But the same link has not been found in the lower doses used in HRT.

How progesterone and estrogen work in the body

Progesterone and estrogen are both steroid hormones that circulate in the bloodstream and directly interact with your DNA. Santoro says that most of the time, estrogen causes one set of reactions and progesterone causes the opposite. For example, estrogen causes the uterine lining to grow while progesterone keeps that growth in check.

During the reproductive years, the two hormones work together to prepare the uterus for a possible pregnancy, David says. “And if there is conception and implantation in the uterus, they both work to maintain the pregnancy.” But during menopause, both hormones diminish. Let’s take a closer look at what each of these hormones do individually:

Estrogen

There’s a reason this is the most well-known female sex hormone. “Estrogen receptors are everywhere in the body and they seem to have effects everywhere,” Santoro says. “When [estrogen] interacts with DNA in bone, it reduces bone resorption [breakdown] and helps prevent osteoporosis. When it interacts with DNA in the uterus, it stimulates growth of the endometrium, the uterine lining, and in the breasts, it also stimulates growth.” This is why you may have noticed your boobs got bigger during certain times of the month when you were younger.

Estrogen naturally declines during menopause because it's produced by the ovaries, which stop functioning around age 50, David explains. This drop in estrogen explains some of the common menopause symptoms during this transition. For example, estrogen binds to receptors in the brain related to temperature regulation. (Less estrogen = you, sweating through your sheets.) And, since estrogen regulates fat distribution and body composition, a lack of the hormone leads to more abdominal and visceral fat accumulation, which is associated with increased cardiovascular disease and metabolic risks. That’s one reason some women seek out a weight-loss program during this life phase.

Progesterone

“The primary function of progesterone is to maintain a pregnancy,” David says. Progesterone is made from the egg that is released during ovulation, so when ovulation stops after menopause, progesterone is no longer produced. But another important function of progesterone is that it “puts the brakes on estrogen’s action in the uterine lining,” Santoro says, which is key to preventing uterine cancer. The drop in progesterone isn’t a concern for women post-menopause since estrogen also naturally declines at this time. But if you’re taking HRT, this is the reason doctors typically prescribe progesterone in addition to estrogen.

HRT with estrogen and progesterone

Combining these two hormones is the most common prescription when it comes to HRT, and for good reason. Here, the doctors explain.

Benefits

Whatever the reason is you’re taking HRT, estrogen is likely what is going to make an impact. “Most of the benefit of hormone therapy comes from the estrogen component,” Santoro says. “Estrogen stops hot flashes very effectively, better than anything else we currently have available.” It also preserves your bone density, improves vaginal dryness and painful intercourse, seems to help with depression in the late menopause transition, and may help prevent heart disease.

The benefit of adding progesterone is to counter estrogen’s impact on the uterus. “The only need for progesterone is to prevent the overgrowth of the lining of the uterus,” Santoro says. “A woman who has a uterus who's taking estrogen needs to take progesterone to prevent that from happening.” If a woman does not have a uterus or gets progesterone via an IUD, there’s no medical need for her to take progesterone — she can just take estrogen alone.

Side effects

Taking a combination of estrogen/progesterone HRT may lead to side effects, including:

• Appetite and weight changes
• Diarrhea
• Headache
• Stomach cramps, pain, or bloating
• Upset stomach
• Vomiting

Combination HRT may also increase the risk of heart attack, stroke, blood clots in the lungs and legs, and breast cancer. That said, most of our understanding regarding breast cancer risk and hormone therapy is from the Women’s Health Initiative data from 2002. “In the group of women who were on combined hormone therapy, there were eight more cases of breast cancer compared to placebo out of 10,000 women,” David says. “In other words, the risk was higher, but the relative number of cases was low.”

HRT with progesterone only

Although not commonly prescribed, here are a few things to know about progesterone-only HRT:

Benefits

Prescribing progesterone alone for menopause symptoms is not a very common practice, and progesterone alone is not FDA approved for this use. However, one 2018 study found that at high doses (300 mg), progesterone can be effective for treating vasomotor symptoms including hot flashes and night sweats. To put that dose into perspective, the amount of progesterone in combination HRT is 150 milligrams.

Because there’s not more data to back it up and also because the higher dose is more likely to cause negative side effects (more on this below), the one time Santoro might prescribe progesterone alone is for women in the early part of the menopause transition who can’t take estrogen due to health issues like a history of endometrial cancer, deep vein thrombosis, stroke, heart attack, or liver disease.

Side effects

The primary side effect of taking progesterone without estrogen, especially at high doses, is breakthrough bleeding: “If some women take progesterone without estrogen, there is this possibility that it can cause the lining of the uterus to become very fragile and it will tend to bleed,” David says, noting that this bleeding is not inherently dangerous.

There’s also progesterone’s impact on energy levels. “One of the desired side effects of progesterone is that it can cause a little bit of sedation,” David says, which is why she tells her patients to take it at bedtime. “It does tend to make patients feel a little bit more relaxed and maybe helps with sleep.”

Types of progesterone HRT

Whether you're taking a combo HRT or progesterone alone, there are four main ways to get it:

Progesterone pills

“The most beneficial way to take progesterone is through oral capsules,” Santoro says. It’s typically dissolved in peanut oil (although sometimes coconut oil is used), and it’s combined with estradiol. Naturally occurring progesterone is preferred over synthetic forms, Santoro says, as it seems to be better tolerated by most people.

Progesterone creams

Patients ask David about creams, but the body can’t absorb enough of the progesterone to get the protective effects for the uterus in this form. “I see patients who are on an estrogen cream for hot flashes and sweats, but if it's combined with a progesterone cream, I get worried that the uterus is not adequately protected,” she says. While it wouldn’t be “harmful” if used alone, it also probably wouldn’t be as beneficial because the body doesn’t absorb progesterone effectively through the skin.

Progesterone injections

While not typically used for HRT, Depo-Provera, a birth control shot that contains progesterone, can be used at higher doses (300 to 400 milligrams instead of the 150 milligrams) to treat hot flashes. David says that the shots last nine to 12 months, but need more research, especially around side effects like an increased risk for stroke.

Progesterone IUDs

An IUD (intrauterine device) is a small device placed in the uterus to prevent pregnancy, and some versions release progesterone into the body. While it's FDA-approved for birth control and managing heavy periods, it’s not currently approved as a treatment for menopause symptoms. That said, an IUD could help protect your uterus against the effects of estrogen.

How to decide if progesterone-only HRT is right for you

In most cases, progesterone-only HRT doesn’t make sense. The one time it might is if a woman cannot take estrogen due to health issues (like a history of breast cancer, stroke, or blood clots) but has hot flashes and wants to try progesterone at a higher dose. “If it works for her, she may wish to continue it but she needs to be aware that there are possible long-term negative effects of this treatment that have just not been studied to date,” Santoro says. Talk with your provider who will take into account your personal health history when deciding which form of HRT is right for you, if any.

The bottom line

Doctors typically prescribe combination HRT containing both estrogen and progesterone, since estrogen delivers the symptom relief while progesterone prevents the uterine wall from growing too thick. While estrogen-only HRT can be used if a woman doesn’t have a uterus due to a hysterectomy or has an IUD, progesterone-only HRT is not commonly prescribed. If a patient is not a good candidate to take estrogen due to their health history but wants to try a higher dose of progesterone for symptoms like hot flashes, their provider will go over any risks and benefits and determine if it’s a good solution.