Estrogen-Only vs Combined HRT: What the Difference Means for You
Estrogen-only vs combined HRT in perimenopause: why progesterone is added, safety profiles, the WHI study in context, breast cancer risk by type, and how to choose.
Why HRT Isn't One Thing
HRT is not a single medication. It's a category that covers several different hormone combinations, delivery methods, and doses. One of the most fundamental distinctions is whether you're taking estrogen alone, or estrogen combined with progesterone or a progestogen. This distinction isn't a minor detail. It determines the safety profile, the side effect pattern, and who the therapy is appropriate for. Understanding which type applies to your situation puts you in a much stronger position to have an informed conversation with your prescriber.
Who Can Take Estrogen Only
Estrogen-only HRT is for people who no longer have a uterus, most commonly because they have had a hysterectomy. The reason this distinction matters is uterine health. Estrogen stimulates the growth of the uterine lining (the endometrium). When there's no progesterone to counterbalance this stimulation and trigger the periodic shedding of that lining, the endometrium can thicken over time, a condition called endometrial hyperplasia, which carries a risk of developing into endometrial cancer. If you have no uterus, this risk doesn't apply, so adding progesterone is unnecessary. Estrogen-only therapy may have a slightly more favorable side effect profile for some people and avoids the additional hormonal effects of progesterone.
Why Progesterone Is Added for Those with a Uterus
If you have a uterus and you're prescribed HRT, you need progesterone alongside estrogen to protect the endometrium. Progesterone (or a synthetic version called a progestogen) works against the endometrium-thickening effect of estrogen, triggering regular shedding and maintaining normal uterine tissue. Combined HRT comes in two main forms: continuous combined, where you take both hormones every day without a break, and sequential combined, where you take estrogen continuously but progesterone is added for part of the month, typically triggering a monthly bleed. Sequential HRT is more commonly used in perimenopause when periods haven't stopped entirely. Continuous combined is more commonly used in post-menopause.
Micronized Progesterone vs Synthetic Progestogens
Not all progesterone is the same, and this matters more than many people realize. Synthetic progestogens, often called progestins, are laboratory-made compounds that mimic progesterone but aren't chemically identical to the hormone your body produces. Micronized progesterone (sold under brand names like Utrogestan or Prometrium) is body-identical, meaning it's chemically the same as the progesterone your ovaries produce. Research, including data from the French E3N cohort study, suggests that micronized progesterone carries a lower associated breast cancer risk than some synthetic progestogens. It also tends to have a more favorable side effect profile, with some evidence of better sleep and fewer mood-related side effects. If you're prescribed combined HRT and have a choice, discussing micronized progesterone with your prescriber is worth the conversation.
Understanding the WHI Study and Its Limitations
Much of the public fear around HRT traces back to the Women's Health Initiative (WHI) study, which reported in 2002 that HRT increased the risk of breast cancer and cardiovascular events. This finding caused a dramatic drop in HRT prescribing that lasted for years and left a generation of women undertreated. What the headlines obscured is that the WHI study used oral conjugated equine estrogen combined with a synthetic progestogen (medroxyprogesterone acetate) in women who were on average 63 years old, more than a decade past natural menopause. Applying those findings to a 48-year-old starting body-identical HRT during perimenopause is not scientifically sound. Subsequent reanalysis of the WHI data, along with a growing body of newer research, has substantially revised the risk picture, particularly for people who start HRT close to menopause.
Breast Cancer Risk by HRT Type
The current evidence suggests that estrogen-only HRT does not significantly increase breast cancer risk and may even be associated with a modest reduction in risk in some analyses. Combined HRT carries a small associated increase in breast cancer risk, and this risk varies by the type of progestogen used. Synthetic progestogens appear to carry a higher associated risk than micronized progesterone. The absolute risk increase is small in younger, healthy women using HRT for a typical duration. However, your personal and family history matters significantly. If you have a first-degree relative who has had breast cancer, or you have other risk factors, the conversation with your prescriber needs to include that context.
Side Effects and Tolerability
Both forms of HRT can cause breast tenderness, bloating, and spotting in the initial adjustment period. Progesterone-containing HRT can also cause mood changes, water retention, headaches, and changes in libido, although micronized progesterone tends to cause fewer of these side effects than synthetic progestogens. If you're on combined HRT and experiencing significant mood disruption or other symptoms, it's worth discussing whether the type of progesterone or the delivery method could be adjusted before concluding that HRT isn't right for you. Delivery method matters too. Transdermal estrogen (patch or gel) avoids the first-pass liver metabolism of oral estrogen and is associated with lower clotting risk.
Making the Decision With Your Prescriber
The right HRT type for you depends on whether you have a uterus, your symptom profile, your personal health history, your family history, and your preferences around side effects and delivery method. This is a decision that warrants a proper consultation rather than a quick choice at the end of a ten-minute appointment. If you feel the conversation has been rushed, or if you were prescribed HRT without a discussion of the options available, asking for a dedicated HRT review appointment is a reasonable request. Menopause specialists have more time and expertise for exactly this conversation. This content is for informational purposes only and does not replace medical advice. Always consult your healthcare provider about your specific situation.
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