What Are Hormone Therapy Combinations?
Hormone therapy combinations are used to treat menopausal symptoms like hot flashes, night sweats, and vaginal dryness by replacing the estrogen and progesterone that the body stops making after menopause. These aren’t one-size-fits-all pills-you need the right mix based on whether you still have your uterus, your age, your health history, and how long it’s been since your last period.
For women who’ve had a hysterectomy, estrogen-only therapy is safe and effective. But if you still have your uterus, you must take progesterone along with estrogen. Without it, estrogen causes the uterine lining to thicken, which can lead to cancer. This isn’t a suggestion-it’s a medical necessity.
Two Main Types of Combination Therapy
There are two main ways to combine estrogen and progesterone: sequential and continuous.
- Sequential combined HRT is for women who are still having periods or just stopped recently. You take estrogen every day, then add progesterone for 10 to 14 days each month. This mimics your old cycle and often causes a monthly bleed, which can feel familiar but isn’t always desired.
- Continuous combined HRT is for women who haven’t had a period for a full year. You take both hormones every single day. No monthly bleed. This is the standard for postmenopausal women who want symptom relief without the hassle of regular bleeding.
Choosing between them isn’t about preference-it’s about your biology. If you’re still cycling, starting continuous therapy can cause unpredictable bleeding. If you’re past menopause, sequential therapy might cause unnecessary monthly bleeds that serve no purpose.
Generic Options: What’s Available and How Much Do They Cost?
Most hormone therapy prescriptions today are generic. Branded versions like Prempro or Climara Pro exist, but they cost 3 to 5 times more. Here’s what you’ll actually get at the pharmacy:
- Estrogen generics: Conjugated estrogens (0.3mg, 0.45mg, 0.625mg) or estradiol (0.5mg, 1mg). These are the most common.
- Progestogen generics: Medroxyprogesterone acetate (2.5mg, 5mg, 10mg) or micronized progesterone (100mg, 200mg).
Prices vary widely. In the U.S., a 30-day supply of generic estradiol and medroxyprogesterone can cost anywhere from $4 to $40, depending on your insurance, pharmacy, and dose. Many plans cover these at $10 or less with a coupon. GoodRx shows that the lowest cash price for a common combination (0.625mg conjugated estrogen + 2.5mg medroxyprogesterone) is around $12 at Walmart or Costco.
Don’t assume the cheapest is best. Micronized progesterone (natural progesterone) is slightly more expensive than synthetic medroxyprogesterone, but studies show it carries a lower risk of breast cancer. For many women, that extra cost is worth it.
Delivery Methods Matter More Than You Think
It’s not just what you take-it’s how you take it. Oral pills are the most common, but they’re not the safest.
When you swallow hormones, they go straight to your liver. This increases your risk of blood clots, stroke, and gallbladder disease. Transdermal options-patches, gels, and sprays-bypass the liver. They deliver hormones directly into your bloodstream through your skin.
Here’s what the data says:
- Oral estrogen increases the risk of venous thromboembolism (VTE) by 2 to 3 times compared to transdermal.
- Transdermal estrogen doesn’t raise stroke risk in women under 60.
- Women with a history of blood clots, migraines with aura, or obesity should avoid oral estrogen entirely.
Transdermal patches are replaced twice a week. Gels are applied daily to clean, dry skin on the arm or thigh. You can’t shower or swim for an hour after applying gel. Sprays are less common but work similarly. The Mirena IUD is another option-it releases progesterone directly into the uterus, so you can take estrogen orally or transdermally without worrying about uterine lining buildup.
Who Should Avoid Hormone Therapy?
Hormone therapy isn’t for everyone. The biggest red flags:
- History of breast cancer
- History of blood clots, stroke, or heart attack
- Unexplained vaginal bleeding
- Liver disease
- Pregnancy
Even if you’re healthy, timing matters. Starting hormone therapy after age 60 or more than 10 years after menopause begins increases the risk of heart disease, stroke, and dementia. The Women’s Health Initiative showed that older women who started HRT years after menopause had higher rates of these problems.
But here’s the flip side: if you’re 52, healthy, and having terrible hot flashes, starting HRT now is very different from starting it at 65. For healthy women under 60, the benefits of symptom relief outweigh the risks-especially if you use transdermal estrogen and micronized progesterone.
Breast Cancer Risk: What the Numbers Really Mean
Most women panic when they hear HRT increases breast cancer risk. But the numbers are smaller than you think.
After 5 years of continuous combined HRT, the risk of breast cancer increases by less than 1 in 1,000 women per year. That’s about 1 extra case per 1,000 users after 5 years. For comparison, being overweight or drinking alcohol daily carries a similar or higher risk.
And not all progesterones are equal. Synthetic progestins like medroxyprogesterone increase breast cancer risk by 2.7% per year of use. Micronized progesterone (natural progesterone) increases it by only 1.9% per year. That’s a 30% lower risk.
If you’re concerned about breast cancer, choose transdermal estrogen + micronized progesterone. Use the lowest dose that works. Reassess every year. Stop when you don’t need it anymore.
How Long Should You Stay on Hormone Therapy?
There’s no fixed rule. Most women take HRT for 2 to 5 years. Some need it longer because symptoms return or are severe.
The North American Menopause Society says to review your treatment every year after the first 3 to 5 years. Ask yourself:
- Are my symptoms under control?
- Do I still feel better on it?
- Have my health risks changed?
Many women stop after a few years because symptoms fade. Others taper slowly to avoid rebound hot flashes. Never stop cold turkey-it can make symptoms worse.
Long-term use (over 10 years) is rare and only considered if symptoms are disabling and no other treatments work. Even then, transdermal estrogen + micronized progesterone is the only safe option.
What About Breakthrough Bleeding?
It’s common-especially in the first 3 to 6 months. About 15% to 20% of women on continuous combined HRT will have spotting or light bleeding early on. That’s normal. Your body is adjusting.
But if bleeding continues past 6 months, or if it’s heavy, painful, or happens after you’ve been stable for months, see your doctor. It could mean your dose is too low, your formulation isn’t right, or something else is going on-like polyps or endometrial thickening.
Don’t ignore it. A simple ultrasound or endometrial biopsy can rule out serious issues.
What’s New in 2026?
Research is moving fast. A new transdermal patch combining estradiol and micronized progesterone was approved by the FDA in 2023. Early data suggests it may lower breast cancer risk even further than older combinations.
Studies like KEEPS show that starting transdermal estrogen within 3 years of menopause may actually protect your heart-reducing artery plaque buildup. This flips the old narrative: HRT isn’t just about symptom relief anymore. For the right woman, at the right time, it might be heart-protective.
Tissue-selective estrogen complexes (TSECs) and selective progesterone receptor modulators (SPRMs) are in late-stage trials. These are designed to give you the benefits of hormones without the cancer risks. They won’t be available yet in 2026, but they’re coming.
Final Checklist: Are You a Good Candidate?
Before starting, ask yourself these questions:
- Do I still have my uterus? (If yes, I need progesterone.)
- Am I under 60 or within 10 years of menopause? (If no, HRT is riskier.)
- Do I have a history of blood clots, stroke, or breast cancer? (If yes, avoid oral estrogen.)
- Am I willing to use transdermal delivery? (Patches or gels are safer.)
- Can I commit to yearly checkups and dose reviews?
If you answered yes to most of these, hormone therapy could be one of the best decisions for your quality of life. If you’re unsure, talk to a menopause specialist-not just your regular doctor. This isn’t a simple prescription. It’s a personalized health strategy.
This is the most comprehensive, no-BS guide to HRT I've ever read. Seriously. Someone finally said it: if you've got a uterus, progesterone isn't optional-it's your body's fire alarm. And transdermal? Non-negotiable. Oral estrogen is basically pouring gasoline on your liver and calling it 'medicine.' I've seen too many women get hit with clots because their doctor was lazy. Stop taking pills. Start using patches. Your veins will thank you.