How Dotti Delivers Estrogen Through Your Skin

You stick a small patch on your belly, and somehow it stops hot flashes. It sounds almost too simple — so how does Dotti actually work?

In this guide, we'll break down the mechanism of action of Dotti (estradiol transdermal system) in plain, everyday language. No medical degree required.

If you're looking for a broader overview, start here: What Is Dotti? Uses, Dosage, and What You Need to Know.

What's Inside the Dotti Patch?

The active ingredient in Dotti is estradiol — specifically, 17β-estradiol. This is a bioidentical hormone, meaning it's chemically identical to the estradiol your ovaries naturally produce.

The patch itself is a small, thin, adhesive square that sticks to your skin. Inside the patch, estradiol is embedded in a matrix (a special adhesive layer) that slowly releases the hormone at a controlled rate over 3 to 4 days.

Step 1: Estradiol Passes Through the Skin

When you apply the Dotti patch to your lower abdomen or upper buttocks, the estradiol in the matrix begins to move from the patch into your skin. This process is called transdermal absorption.

Your skin isn't just a barrier — it has tiny blood vessels (capillaries) just below the surface. Estradiol molecules are small enough to pass through the outer layers of skin and reach these blood vessels.

This is why application site matters:

• Lower abdomen and upper buttocks work best because the skin is relatively thin and well-supplied with blood vessels
• Breasts should be avoided — direct estrogen exposure to breast tissue is not recommended
• Oily, broken, or irritated skin can affect absorption

Step 2: Estradiol Enters the Bloodstream

Once estradiol passes through the skin into the capillaries, it enters your bloodstream directly. This is one of the biggest advantages of a transdermal patch over an oral pill.

Why Does This Matter?

When you take oral estradiol (a pill), it goes through your digestive system and passes through the liver before reaching the rest of your body. This is called first-pass metabolism. The liver processes the estradiol and converts some of it into other compounds. This can:

• Increase production of clotting factors (raising blood clot risk)
• Affect cholesterol and triglyceride levels
• Reduce the amount of active estradiol that reaches your tissues

With Dotti, estradiol goes directly from the skin to the blood — bypassing the liver entirely. This means:

• More consistent estradiol levels throughout the day
• Lower impact on clotting factors
• Potentially fewer metabolic side effects

This liver bypass is a key reason why the FDA removed the black box warning from transdermal estradiol in November 2025 — the safety profile is different from oral estrogen.

Step 3: Estradiol Binds to Estrogen Receptors

Once in the bloodstream, estradiol travels throughout the body and binds to estrogen receptors — special proteins found on cells in many different tissues. Think of estrogen receptors like locks, and estradiol as the key that fits them.

Estrogen receptors are found in:

• The brain — specifically the hypothalamus, which controls body temperature
• The uterus and vaginal tissues
• Bones
• Blood vessels
• Skin
• The heart

When estradiol binds to these receptors, it activates specific cellular responses that depend on the tissue type.

How This Relieves Menopause Symptoms

Now let's connect the science to what you actually feel:

Hot Flashes and Night Sweats

During menopause, dropping estrogen levels disrupt the hypothalamus — the part of your brain that acts as your body's thermostat. Without enough estrogen, the hypothalamus becomes overly sensitive to small changes in body temperature. It thinks you're overheating and triggers a hot flash: blood vessels dilate, you sweat, your heart races.

Dotti restores estradiol to the hypothalamus, resetting the thermostat. Your brain stops overreacting to normal temperature fluctuations, and hot flashes decrease in frequency and severity.

Vaginal Dryness and Atrophy

Estrogen keeps vaginal tissues thick, elastic, and lubricated. When estrogen drops, these tissues become thin and dry — a condition called vaginal atrophy. Dotti provides systemic estrogen that helps restore blood flow and moisture to vaginal tissues.

Bone Loss (Osteoporosis)

Estrogen helps regulate the activity of cells that build and break down bone. Without enough estrogen, bone breakdown outpaces bone building — leading to osteoporosis. By restoring estradiol levels, Dotti helps maintain bone density and reduces the risk of fractures.

How Long Does It Take to Work?

You won't feel better overnight. Here's a general timeline:

• 1-2 weeks: Estradiol levels begin to rise and stabilize
• 2-4 weeks: Some women notice a reduction in hot flashes
• 4-12 weeks: Most women see significant improvement in vasomotor symptoms
• 3-6 months: Full benefits for vaginal atrophy and bone density protection become apparent

If you haven't noticed improvement after 8 to 12 weeks, talk to your doctor. Your dose may need adjusting. Dotti comes in five dose strengths — from 0.025 mg/day to 0.1 mg/day.

Steady-State Delivery: Why Patches Are Different

One of the unique things about Dotti is its steady-state delivery. Unlike a pill that creates a spike in estradiol levels after you swallow it (followed by a gradual decline), the Dotti patch delivers a consistent amount of estradiol 24 hours a day, for 3 to 4 days straight.

This steady delivery means:

• Fewer ups and downs in hormone levels
• More consistent symptom relief
• Potentially fewer side effects related to hormone fluctuations (like mood swings or headaches)

When you change the patch every 3-4 days, the new patch picks up where the old one left off, maintaining steady estradiol levels in your blood.

What Happens When You Remove the Patch?

When you take off a Dotti patch, estradiol levels in your blood begin to decline gradually. They don't drop instantly — there's still some estradiol stored in the skin at the application site that continues to absorb for a short time. This is why the twice-weekly schedule works: it keeps levels relatively stable.

If you stop using Dotti entirely (under your doctor's guidance), estradiol levels will return to your baseline menopausal levels within a few days, and symptoms may return.

Factors That Can Affect How Well Dotti Works

Several things can influence how much estradiol you actually absorb from the patch:

• Application site: Abdomen and buttocks absorb best. Avoid areas with thick skin, hair, or skin folds.
• Skin condition: Lotions, oils, or sunscreen on the application area can interfere with absorption.
• Heat: Saunas, hot tubs, and heating pads over the patch can temporarily increase absorption, potentially causing side effects.
• Medications: Drugs that affect CYP3A4 enzymes can change estradiol levels. See our drug interactions guide.

Dotti vs. Other Delivery Methods

Understanding how Dotti works helps explain why some women prefer patches over other forms of estrogen:

• Oral estradiol (pills): Goes through the liver — more convenient but higher clotting risk
• Estradiol gel (EstroGel, Divigel): Also transdermal but requires daily application. Similar benefits to patches but less convenient for some.
• Vaginal estrogen: Treats local symptoms only (vaginal atrophy) — doesn't provide systemic relief for hot flashes or bone protection

For alternatives during shortages, see: Alternatives to Dotti.

Final Thoughts

Dotti works by delivering bioidentical estradiol through your skin into your bloodstream, bypassing the liver and providing steady hormone levels 24/7. This estradiol then binds to estrogen receptors throughout your body — calming your brain's thermostat, protecting your bones, and restoring vaginal health.

It's elegantly simple science, packaged in a tiny patch.

If you've been prescribed Dotti and need help finding it, visit MedFinder to check availability near you. For side effect info, see our side effects guide.