Hormone Therapy Combinations: Generic Choices and Considerations

When women start experiencing hot flashes, night sweats, or mood swings during menopause, hormone therapy can make a real difference. But not all hormone treatments are the same. The right combination depends on your body, your history, and what you’re trying to avoid as much as what you’re trying to fix. Many women assume hormone therapy means taking one pill every day - but that’s only one option. There are different types of combinations, delivery methods, and generic versions that can change everything - from your risk of blood clots to whether you’ll have monthly bleeding.

Why Combination Therapy Matters

If you still have your uterus, you can’t take estrogen alone. It’s not safe. Estrogen makes the lining of your uterus grow. Left unchecked, that growth can turn into cancer. That’s why doctors combine estrogen with progestogen - a synthetic or natural form of progesterone - to protect the uterine lining. This isn’t optional. It’s a medical necessity.

For women who’ve had a hysterectomy, estrogen-only therapy is fine. But for the rest, the combination is non-negotiable. The key is choosing the right kind of combination and the right way to take it.

Two Main Types of Combined HRT

There are two main ways to combine estrogen and progestogen: 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 progestogen for the last 10 to 14 days of the month. This mimics your natural cycle. You’ll likely get a withdrawal bleed - kind of like a period - each month. It’s designed for women in perimenopause or early menopause who still have some hormonal rhythm left.

Continuous combined HRT is for women who haven’t had a period for a full year. You take both hormones every single day, with no breaks. There’s no monthly bleed. This is the go-to for most postmenopausal women. It’s simpler, and studies show it lowers the risk of colon cancer by about 18% and type 2 diabetes by 21%, based on data from the Women’s Health Initiative.

Choosing between them isn’t about preference - it’s about your body’s stage. Taking continuous HRT too early can cause unpredictable bleeding. Taking sequential HRT after a year without periods might not control symptoms as well.

Generic Options You Can Actually Use

Most hormone therapy prescriptions today are generic. That’s because they’re cheaper - sometimes much cheaper - than brand names. And they work just as well.

Common generic estrogens include:

• Conjugated estrogens - 0.3mg, 0.45mg, or 0.625mg tablets. These are derived from horse urine and have been around for decades.
• Estradiol - 0.5mg or 1mg tablets. This is the same hormone your body naturally makes. Many doctors prefer it because it’s more bioidentical.

Common generic progestogens:

• Medroxyprogesterone acetate - 2.5mg, 5mg, or 10mg tablets. This is a synthetic progestin. It’s widely used but linked to slightly higher breast cancer risk.
• Micronized progesterone - 100mg or 200mg capsules. This is natural progesterone, made from plant sources. It’s gentler on the breasts and may lower cancer risk compared to synthetic versions.

In the U.S., these generics cost between $4 and $40 a month, depending on your insurance. In the UK, many are available for free on the NHS. The price difference between branded and generic can be huge - sometimes over 80%.

Delivery Methods: Patches, Gels, and More

How you take your hormones matters as much as what you take.

Oral pills are the most common. But they go through your liver first. That’s a problem. The liver reacts by increasing clotting factors. That’s why oral estrogen raises your risk of blood clots by 2 to 3 times compared to skin-based methods.

Transdermal options - patches, gels, and sprays - skip the liver. They go straight into your bloodstream. That means:

• Lower risk of blood clots
• Lower risk of stroke, especially after age 60
• More stable hormone levels

Patches are changed twice a week. Gels are applied daily to the arm or thigh. Sprays go on the forearm. All require you to avoid skin-to-skin contact for an hour after application - especially important if you live with someone.

In the UK and parts of Europe, over 60% of HRT prescriptions are transdermal. In the U.S., it’s closer to 35%. Why? Cost and habit. But that’s changing. More doctors are pushing for patches and gels - especially for women over 50 or with a history of clots.

Who Should Avoid Hormone Therapy?

HRT isn’t for everyone. You should not start it if you have:

• A history of breast cancer
• Unexplained vaginal bleeding
• Active liver disease
• History of blood clots, stroke, or heart attack

Even if you don’t have those, timing matters. Starting HRT after age 60 - or more than 10 years after menopause - increases your risk of heart disease, stroke, and dementia. That’s why experts say: start early, use the lowest dose, and don’t stay on it longer than needed.

The Women’s Health Initiative showed that for healthy women under 60 or within 10 years of menopause, the benefits outweigh the risks. For women over 60, the balance flips.

Long-Term Risks and What the Data Really Says

The biggest fear around HRT is breast cancer. Let’s be clear: the risk is small, but real.

Using combined HRT for more than five years increases breast cancer risk by less than 1 in 1,000 women per year. That’s tiny - but it adds up. The risk is higher with synthetic progestins like medroxyprogesterone acetate. With micronized progesterone, the risk is lower - about 1.9% per year versus 2.7% for synthetic versions.

Estrogen-only therapy doesn’t raise breast cancer risk much - but again, only if you’ve had a hysterectomy. For women with a uterus, skipping progestogen is dangerous.

Heart risks are also tied to delivery method. Oral estrogen increases stroke risk by about 39% in women over 60. Transdermal estrogen doesn’t. That’s why many doctors now recommend patches or gels for older women.

What to Expect When You Start

Most women don’t feel better overnight. It takes 3 to 6 months to find the right dose and delivery method. Side effects like bloating, breast tenderness, or mood swings are common at first. They usually fade.

Breakthrough bleeding happens in 15 to 20% of women during the first 6 months - especially with sequential therapy. That’s normal. But if it keeps happening after six months, you need to see your doctor. It could mean the dose is too low, the type of progestogen isn’t right, or something else is going on.

Don’t stop because of bleeding. Don’t switch brands because you’re frustrated. Work with your provider. Adjust slowly. Keep a symptom journal. It helps.

The Future of Hormone Therapy

New options are coming. In 2023, the FDA approved a new transdermal patch that combines estrogen and progesterone in one patch. Early data suggests it may lower breast cancer risk even more than older combinations.

Researchers are also testing tissue-selective estrogen complexes (TSECs) and selective progesterone receptor modulators (SPRMs). These are designed to give symptom relief without affecting breast or uterine tissue the same way traditional hormones do.

But for now, the best tools we have are the ones already here: low-dose, transdermal, generic, and personalized.

How to Decide What’s Right for You

Ask yourself these questions:

• Have I had a hysterectomy?
• Am I under 60 or within 10 years of my last period?
• Do I have a history of blood clots, stroke, or breast cancer?
• Am I willing to apply a gel daily or change a patch twice a week?
• Can I afford or access transdermal options?

Talk to your doctor about your symptoms, your risks, and your goals. Don’t let fear stop you - but don’t let convenience drive your choice either.

The goal isn’t to take hormones forever. It’s to get through the worst of menopause safely, then step back when you can.