Bioidentical vs. Synthetic HRT: The Guide Every Woman Needs

The decision to start hormone replacement therapy is not something women make on a whim. There are still fears that this treatment isn’t safe (it is for most women), uncertainty of the benefits, and even lingering negative associations from brutal birth control experiences. 

But hormone therapy can support a lot of women through the menopause transition. Not only does it help address its most pressing symptoms (like hot flashes and sleep1), but it can also support long-term health. It’s also not a one-size-fits-all approach. 

The hormones used, when you start them, and how you take them (via pills, patches, pellets, or creams) are highly personalized to you, your lab values, your symptoms, and your goals. 

Hormone therapy2 supplies the body with hormones that naturally decline during perimenopause and menopause (like estrogen, progesterone, and sometimes testosterone). 

“Traditional hormone therapy was always more geared towards synthetic hormones—hormones designed to look similar to the body’s compounds, but not exactly the same,” says Lynn Mason, N.P. “Bioidentical hormones changed that. They’re the exact organic compound the body produces.” 

Well, hormones are chemical messengers. They’re released into the bloodstream and travel throughout the body to reach different tissues. Think of the receptors as locks and the hormone as keys. 

In fact, “Some non-bioidentical hormones bind more tightly to those receptors, which makes them harder to manage,” says Wendie Trubow, M.D., MBA. 

Mason agrees and notes, “With synthetic hormones… the chemical structure is similar to the body’s own, but not identical. That means the body has to convert it before it can be used, and that conversion can sometimes trigger inflammation.”

Hormone therapies—including some bioidentical options—are approved by the Food and Drug Administration4 (FDA) and considered safe when used as directed under the care of licensed practitioners.  

All compounded medications5 (including synthetic or bioidentical hormone therapy) are made specifically by a pharmacy for an individual patient. In these cases, creams, lozenges (or troches), and pellets (that are tiny, rice-sized cylinders placed under the skin) provide customized doses and/or combinations of hormones. 

While the ingredients may be FDA approved, the final compounded product isn’t due to it not meeting the criteria mentioned above. That said, many practitioners (like Mason) like the personalization that compounded options provide. 

What’s important is working with a qualified practitioner to come up with a plan that suits your goals and preferences.  

A personalized approach to hormone therapy means taking your lab values and symptoms into consideration both before menopause (perimenopause) and after that one-year mark of not getting your period (menopause and postmenopause). 

“Menopause is defined as twelve full months with no menses. But you could go 364 days without a period and then have one, so technically you’re not in menopause yet,” says Trubow. “We don’t want women to suffer through that entire stretch, so we start treatment based on symptoms, not just the calendar.”

Trubow and Mason share a few insights they consider when recommending starting (or waiting) for hormone therapy. 

“For a lot of women, if their adrenals aren't optimized, the first hormone many women benefit from is bioidentical progesterone, which supports sleep and relaxation,” says Trubow. “It’s usually given for two weeks each cycle.” 

Research shows that during perimenopause, many women actually have higher and erratic estradiol levels6 but lower progesterone, which can drive symptoms like hot flashes, sleep disturbances, breast tenderness, and mood changes. 

Depending on her patient, Mason may start with recommending testosterone therapy. 

“When women start noticing weight gain, night sweats, trouble with cognition or clear thinking, lower sex drive, fatigue, or slower recovery from exercise, we often check both total and free testosterone to see where they’re at and how we can optimize it,” says Mason. 

Based on symptoms and lab results, “introducing testosterone earlier—late 30s or early 40s, even before menopause can reduce symptoms, and make the transition into perimenopause and menopause smoother,” says Mason. 

The timing of estradiol (the bioidentical form of estrogen) can be tricky. Adding this therapy when the ovaries are still producing meaningful amounts of the hormone can have some side effects. 

“If you have too much estradiol, you’ll feel it: you get irritable, your breasts are tender, you feel bloated—basically classic PMS,” says Trubow. “Too much estradiol in a woman who’s still ovulating can even cause continuous bleeding. It can be a really frustrating, ‘crazy-making’ time, which is why hormone therapy has to be carefully dialed in.”

So, when can estradiol treatment be started? Trubow says that she may start to layer in estradiol once a woman has gone at least three months without a period and that the dose may have to be adjusted based on how you’re feeling. 

Hormone therapy isn’t just one treatment. Instead, it's an individualized plan to help you feel and function your best. While the experts we interviewed here favor bioidentical options, hormone therapy in general can be safe and effective when prescribed and monitored by a qualified practitioner. 

“I think the most important thing is for women to be completely transparent with their provider about how they’re feeling,” says Mason. “Go over all the symptoms, make sure labs are being checked, and that they’re being heard. There’s nothing worse than feeling like you’re not yourself and no one is listening.”