Menopause Myth #11: Oral vs. Transdermal HRT: Why the Route Matters More Than You Think

“Does it really matter whether HRT is a tablet or a patch?”

A 53-year-old woman asks me this during a consultation. She’s been prescribed oral HRT (oestrogen tablets) by her GP. She’s read online that patches might be safer but isn’t sure if it’s worth the hassle of switching.

“They’re both just oestrogen, right?” she asks. “Surely it’s the same thing?”

No. It’s not the same thing.

The route of HRT administration — how the hormone enters your body — changes the safety profile dramatically.

This isn’t a minor detail or personal preference. It’s one of the most important decisions in HRT prescribing — and one that many healthcare providers and women don’t fully understand.

Let me explain why this matters so much.

The Two Main Routes of Oestrogen Administration

When we talk about HRT “route,” we mean how the oestrogen gets into your bloodstream.

Oral HRT (Tablets)

What it is:

  • Oestrogen in tablet form
  • Swallowed with water
  • Common brands in UK: Elleste Solo, Progynova, Zumenon, Premique (combined), Femoston (combined)

How it works:

  • You swallow the tablet
  • It’s absorbed from your digestive system (stomach and intestines)
  • It travels via the portal vein directly to the liver first
  • The liver metabolizes (processes) the oestrogen before it enters general circulation
  • After liver processing, oestrogen enters the bloodstream and travels throughout the body

This liver-first route is called “first-pass metabolism.”

Transdermal HRT (Patches, Gel)

What it is:

  • Oestrogen applied to the skin
  • Patches: Adhesive patches applied to skin (abdomen, buttocks, thighs), changed once or twice weekly
  • Gel: Applied to skin (arms, inner thighs) once daily

Common brands in UK:

  • Patches: Evorel, Estradot, FemSeven
  • Gel: Oestrogel, Sandrena

How it works:

  • Oestrogen is applied to the skin
  • It’s absorbed through the skin directly into the bloodstream
  • Bypasses the liver — goes straight into general circulation
  • Delivers steady levels of oestrogen throughout the day
  • No first-pass metabolism

This bypass of the liver is the critical difference.

Why First-Pass Metabolism Matters

When oral oestrogen passes through the liver, several things happen:

The Liver Produces Proteins and Clotting Factors

The liver is triggered to produce various proteins, including:

Clotting factors:

  • Increased production of factors that promote blood clotting
  • Includes: Factor VII, Factor VIII, fibrinogen
  • Simultaneously decreases natural anticoagulants (proteins that prevent clotting)

Result: The balance shifts toward a pro-thrombotic state — meaning blood is more likely to clot.

This is why oral oestrogen increases VTE (venous thromboembolism) risk — blood clots in veins, typically in legs (deep vein thrombosis/DVT) or lungs (pulmonary embolism/PE).

Angiotensinogen:

  • Precursor to angiotensin (compound that raises blood pressure)
  • Increased production can affect blood pressure regulation
  • This is why oral oestrogen can raise blood pressure in some women

Sex hormone-binding globulin (SHBG):

  • Binds to sex hormones in the blood
  • Reduces amount of free (active) testosterone and oestrogen
  • Can affect symptom control and libido

C-reactive protein (CRP):

  • Marker of inflammation
  • Oral oestrogen increases CRP
  • Clinical significance debated, but may affect cardiovascular risk assessment

Variable Absorption and Metabolism

Oral oestrogen absorption is affected by:

  • Digestive function (how well your gut absorbs medications)
  • Food in stomach (taking with or without food affects absorption)
  • Other medications (interactions with gut absorption)
  • Liver enzyme activity (varies between individuals and can be affected by other medications, alcohol, etc.)

Result: More variable blood levels of oestrogen — peaks and troughs throughout the day rather than steady state.

Higher Total Dose Required

Because of liver metabolism, some oestrogen is broken down before reaching general circulation.

This means oral HRT requires higher total doses to achieve the same blood levels as transdermal.

Example:

  • Oral estradiol 2 mg/day ≈ Transdermal patch 100 mcg/day

The oral dose looks much higher because you need more to compensate for liver breakdown.

Transdermal HRT: What’s Different

When oestrogen is applied to the skin (patches or gel):

Bypasses First-Pass Liver Metabolism

  • Absorbed through skin directly into bloodstream
  • Does NOT go through the liver first
  • Liver doesn’t produce the same clotting factors, angiotensinogen, or other proteins triggered by oral oestrogen
  • No increase in pro-thrombotic state

Result: Transdermal oestrogen does NOT increase VTE risk, does NOT raise blood pressure, has different metabolic effects.

Steady Hormone Levels

  • Continuous absorption throughout the day (patches deliver steadily; gel absorbs quickly but applied daily)
  • No peaks and troughs
  • More stable blood levels

Result: More consistent symptom control, fewer side effects from fluctuating levels.

Lower Doses Needed

  • Because there’s no liver breakdown, you need less total oestrogen
  • Patches are measured in micrograms (mcg) rather than milligrams (mg)
  • Don’t be alarmed that patch doses “look” lower — they deliver steady state without liver loss

Predictable Absorption

  • Not affected by digestive function or food
  • Not affected by gut medications
  • More consistent between individuals

Result: More predictable effects and easier to optimize dosing.

The Safety Differences: What the Evidence Shows

This isn’t theoretical. Large, well-conducted studies consistently show significant safety differences between oral and transdermal HRT.

VTE (Blood Clot) Risk

This is the most important safety difference.

ORAL OESTROGEN:

  • Increases VTE risk approximately 2-3 times compared to not using HRT
  • Absolute risk remains relatively low (approximately 2-3 extra cases per 1,000 women per year)
  • Risk higher at higher doses
  • Risk highest in first year of use

TRANSDERMAL OESTROGEN:

  • NO increased VTE risk — equivalent to not using HRT
  • Multiple large studies confirm this
  • No increased risk even at higher doses (within therapeutic range)
  • No increased risk even in first year of use

Key studies:

French E3N cohort study (over 80,000 women):

  • Oral oestrogen: Significantly increased VTE risk
  • Transdermal oestrogen: NO increased VTE risk
  • This was a landmark study that changed prescribing guidelines

UK case-control studies:

  • Consistently show oral oestrogen increases VTE risk 2-3 fold
  • Transdermal oestrogen: No increased risk

Mechanism: The difference is explained by first-pass liver metabolism → oral oestrogen triggers clotting factor production → transdermal doesn’t.

Clinical implication: For VTE risk, transdermal oestrogen is dramatically safer than oral.

Stroke Risk

ORAL OESTROGEN:

  • Small increase in stroke risk (approximately 1.3-1.5 fold increase)
  • Absolute risk increase is small but measurable
  • Risk appears dose-dependent

TRANSDERMAL OESTROGEN:

  • No significant increase in stroke risk at standard doses
  • Some studies suggest neutral or possibly protective effect when started early

Clinical implication: Transdermal appears safer for stroke risk, particularly in women with cardiovascular risk factors.

Blood Pressure

ORAL OESTROGEN:

  • CAN raise blood pressure in some women (not all)
  • Effect related to increased angiotensinogen production by liver
  • Particularly problematic if pre-existing hypertension

TRANSDERMAL OESTROGEN:

  • Does NOT raise blood pressure
  • Bypasses the liver pathway that affects blood pressure regulation
  • Safe for women with well-controlled hypertension

Clinical implication: Transdermal is preferred for women with cardiovascular risk factors including hypertension.

Cardiovascular Disease Risk

The relationship between HRT and cardiovascular disease is complex and depends on multiple factors (age, time since menopause, route, etc.).

General findings:

When started early (within 10 years of menopause or before age 60):

  • Transdermal oestrogen: Neutral or possibly protective cardiovascular effect
  • Oral oestrogen: Findings more mixed, some studies show slight increase in cardiovascular events

When started late (>10 years post-menopause or after age 60):

  • Both oral and transdermal may increase cardiovascular risk
  • Transdermal still safer than oral

Clinical implication: When HRT is appropriate (started early), transdermal has better cardiovascular safety profile than oral.

Metabolic Effects

Both oral and transdermal oestrogen have beneficial metabolic effects:

  • Improve insulin sensitivity
  • Favorable effects on lipid profile (increase HDL “good” cholesterol, decrease LDL “bad” cholesterol)

However, oral oestrogen has some less favorable effects due to liver metabolism:

  • Increases triglycerides more than transdermal (clinical significance unclear)
  • Increases CRP (inflammatory marker)
  • Increases SHBG more (which can affect testosterone levels and libido)

Transdermal has “cleaner” metabolic profile without the liver-mediated effects.

Current Guidelines: What Do They Recommend?

Given the clear safety differences, what do evidence-based guidelines recommend?

NICE Guidelines (2015)

The UK’s National Institute for Health and Care Excellence states:

“Transdermal rather than oral HRT should be used for women with increased risk of VTE.”

Women with increased VTE risk include:

  • Obesity (BMI >30)
  • Personal or family history of VTE
  • Thrombophilia (genetic clotting disorders)
  • Immobility
  • Significant comorbidities

NICE also recommends transdermal for women with cardiovascular risk factors including hypertension.

British Menopause Society

The UK’s specialist menopause organization states:

“Transdermal oestrogen is preferred to oral oestrogen.”

Particularly for women with:

  • Obesity (BMI >30)
  • Hypertension
  • Diabetes
  • Migraines (especially with aura)
  • History of VTE
  • Over age 60
  • Starting HRT >10 years post-menopause
  • Cardiovascular risk factors

The British Menopause Society essentially recommends transdermal as first-line for most women.

International Menopause Society

The global authority on menopause care recommends:

Transdermal oestrogen for:

  • Women at increased cardiovascular risk
  • Women with VTE risk factors
  • Women over 60
  • Starting HRT >10 years post-menopause

The pattern is clear: International guidelines consistently recommend transdermal oestrogen as safer and preferred over oral for most women.

Who Should Definitely Use Transdermal (Not Oral)

Some women should NOT use oral oestrogen — transdermal is strongly preferred (or HRT is contraindicated if risks are very high):

Absolute Preference for Transdermal:

Obesity (BMI >30):

  • Significantly increases VTE risk
  • Oral oestrogen further increases risk
  • Transdermal does NOT increase VTE risk
  • All women with BMI >30 should use transdermal, not oral

Personal history of VTE:

  • Previous DVT or PE
  • Even if provoked (e.g., after surgery or long flight), caution needed
  • Oral oestrogen significantly increases recurrence risk
  • Transdermal may be considered with careful assessment (doesn’t increase VTE risk)

Strong family history of VTE:

  • First-degree relative with VTE (especially if unprovoked or at young age)
  • May indicate genetic thrombophilia
  • Oral oestrogen contraindicated
  • Transdermal may be appropriate with thrombophilia screening

Thrombophilia (genetic clotting disorders):

  • Factor V Leiden, Prothrombin gene mutation, etc.
  • Oral oestrogen contraindicated
  • Transdermal may be considered (doesn’t increase VTE risk) but requires specialist assessment

Migraines with aura:

  • Slightly increases stroke risk
  • Oral oestrogen may further increase stroke risk
  • Transdermal preferred (doesn’t appear to increase stroke risk)

Hypertension:

  • Oral can raise blood pressure
  • Transdermal does not
  • If blood pressure well-controlled, transdermal can be used safely

Diabetes:

  • Increases cardiovascular risk
  • Transdermal has better cardiovascular profile
  • Strongly preferred

Age >60 or >10 years post-menopause:

  • Cardiovascular risk increases with age and time since menopause
  • If HRT started/continued in this group, transdermal strongly preferred

Current smokers:

  • Smoking dramatically increases cardiovascular and VTE risk
  • Oral HRT should NOT be used
  • Transdermal may be considered (but smoking cessation should be strongly encouraged)

Multiple cardiovascular risk factors:

  • Combination of: hypertension, high cholesterol, diabetes, obesity, smoking, family history
  • Increases cardiovascular risk
  • Transdermal preferred

Are There Any Advantages to Oral HRT?

Given the safety advantages of transdermal, why would anyone use oral HRT?

There are a few scenarios where oral might be chosen:

Skin Sensitivity or Allergy

Some women develop skin reactions to patches:

  • Redness, itching, rash at patch site
  • Can be severe enough to make patches intolerable
  • Different patch brands can be tried (adhesives differ)
  • Gel can be tried (doesn’t have adhesive, less likely to cause reactions)

If both patches AND gel cause skin issues (rare), oral may be the only option.

Practical/Lifestyle Reasons

Some women find patches or gel inconvenient:

  • Patches can come off (with swimming, sweating, hot baths)
  • Patches visible (some women self-conscious)
  • Gel requires waiting time before dressing, no swimming immediately after application, careful about partner/children contact while gel still wet

For some women, a daily tablet is simply easier.

However, convenience shouldn’t override safety — if you have risk factors, transdermal is still strongly recommended even if less convenient.

Cost (in Some Healthcare Systems)

In the UK NHS, both oral and transdermal HRT are available on prescription with the same prescription charge.

In some other countries, transdermal may be more expensive or not covered by insurance. This can be a barrier.

Cost should be weighed against safety — but financial constraints are real.

Prescriber Preference/Familiarity

Some prescribers are more familiar with oral HRT and default to prescribing what they know.

This is NOT a good reason — prescribers should follow evidence-based guidelines and prescribe the safest option.

What About Progesterone Route?

We’ve been discussing oestrogen, but what about progesterone?

If you have a uterus, you need progesterone alongside oestrogen to protect the endometrium (lining of the womb) from overstimulation by unopposed oestrogen.

Progesterone Routes:

Oral micronized progesterone:

  • Body-identical progesterone in capsule form
  • Brand name in UK: Utrogestan
  • Taken daily (continuous combined) or for 12-14 days per month (cyclical/sequential)
  • Preferred progesterone — best evidence for safety (particularly breast cancer risk)

Progesterone IUS (intrauterine system):

  • Mirena coil (levonorgestrel-releasing IUS)
  • Provides local endometrial protection
  • Systemically absorbed but at lower levels
  • Can be used alongside oestrogen (oral OR transdermal)
  • Particularly useful if you also need contraception or have heavy periods

Combined patches:

  • Patches that deliver BOTH oestrogen and progestogen
  • E.g., Evorel Conti, Evorel Sequi, FemSeven Conti
  • Progestogen is synthetic (norethisterone or levonorgestrel)
  • Convenient (one patch provides both hormones)
  • BUT: Synthetic progestogens may have less favorable risk profile than body-identical progesterone

Combined tablets:

  • Deliver both oestrogen and progestogen orally
  • Progestogen usually synthetic

For breast cancer risk, body-identical micronized progesterone (Utrogestan) appears safest.

Ideal combination for safety: Transdermal oestrogen + oral micronized progesterone (Utrogestan)

How to Switch from Oral to Transdermal

If you’re currently on oral oestrogen and want to switch to transdermal (or your prescriber recommends switching), how does it work?

The Process:

Step 1: Discuss with your prescriber

Explain:

  • You’ve learned about safety differences
  • You’d like to switch to transdermal
  • Ask their support for the switch

Most prescribers will support this — it aligns with current guidelines.

Step 2: Determine equivalent dose

Your prescriber will calculate the equivalent transdermal dose.

Approximate equivalents:

  • Oral estradiol 1 mg/day ≈ Transdermal 50 mcg patch
  • Oral estradiol 2 mg/day ≈ Transdermal 100 mcg patch

Step 3: Stop oral, start transdermal

Usually:

  • Stop oral oestrogen on last day of packet
  • Start transdermal patch the next day
  • OR: Apply first patch on last day of oral tablets, then continue with patches

No break is needed between stopping oral and starting transdermal.

Step 4: Continue progesterone unchanged

If you’re taking progesterone (Utrogestan or other), continue as before. The progesterone stays the same; only the oestrogen route changes.

If you’re on combined (oestrogen + progestogen) tablets, discuss with prescriber:

  • Switch to transdermal oestrogen patch
  • Add separate oral progesterone (Utrogestan)
  • OR: Use Mirena coil for endometrial protection

Step 5: Monitor

After switching:

  • Symptoms may change slightly as your body adjusts (give it 2-4 weeks)
  • Most women feel no different or feel BETTER (more stable hormone levels)
  • Side effects from oral (nausea, breast tenderness) often improve
  • Symptom control usually remains good or improves

Step 6: Review after 3 months

Check in with prescriber:

  • How are symptoms?
  • Any side effects?
  • Is patch staying on well?
  • Any skin reactions?
  • Any dose adjustment needed?

Switching is usually straightforward and well-tolerated.

Practical Aspects: Patches vs. Gel

Both patches and gel are “transdermal” — they bypass the liver. But which is better?

There’s no clear winner — it’s personal preference.

Patches:

Advantages:

  • Apply once or twice weekly (less frequent than daily gel)
  • Don’t have to think about it daily
  • Precise dosing (each patch delivers fixed amount)
  • Can’t forget to apply (visual reminder on your skin)

Disadvantages:

  • Can come off (with sweating, swimming, hot baths)
  • Visible (some women self-conscious)
  • Can cause skin irritation or allergic reaction to adhesive
  • Less flexible dosing (come in fixed doses — 25, 50, 75, 100 mcg)

Tips for patches:

  • Apply to clean, dry skin (below waist — abdomen, buttocks, thighs)
  • Avoid areas where clothing rubs (waistband)
  • Rotate sites (don’t use same spot twice in a row)
  • If edges lift, can secure with medical tape
  • Different brands have different adhesives — if one irritates, try another

Gel:

Advantages:

  • No adhesive (less likely to cause skin reactions)
  • Not visible once absorbed
  • Flexible dosing (can adjust by pumps/sachets for fine-tuning)
  • Doesn’t come off with swimming/bathing (once absorbed)

Disadvantages:

  • Daily application required (easier to forget)
  • Must wait for gel to dry before dressing (5-10 minutes)
  • Must avoid partner/children contact while gel still wet (oestrogen can transfer)
  • Can’t swim immediately after application (should wait 1 hour)

Tips for gel:

  • Apply to clean, dry skin (usually arms or inner thighs)
  • Spread thinly over large area (don’t rub into one small spot)
  • Allow to dry before dressing
  • Wash hands after application
  • Apply at consistent time daily (e.g., after morning shower)

Both are equally effective. Choose based on lifestyle and personal preference.

Some women start with patches (easier) and switch to gel if skin reactions develop.

What You Should Do

If You’re Not Yet on HRT:

If you’re considering starting HRT:

  • Request transdermal (patch or gel) rather than tablets
  • Specifically say: “I’d like transdermal oestrogen — patches or gel — as it has a better safety profile than oral”
  • If your prescriber suggests oral tablets, ask why transdermal isn’t being recommended
  • If you have ANY risk factors (obesity, hypertension, over 60, etc.), transdermal is strongly preferred

Don’t accept oral oestrogen without discussion of why transdermal isn’t appropriate.

If You’re Already on Oral HRT:

If you’re currently taking oral oestrogen tablets:

Ask yourself:

  • Do I have any VTE risk factors? (obesity, family history, previous VTE, immobility, etc.)
  • Do I have cardiovascular risk factors? (hypertension, diabetes, high cholesterol, smoking, etc.)
  • Am I over 60 or more than 10 years post-menopause?
  • Do I have migraines (especially with aura)?

If YES to any of the above, you should discuss switching to transdermal with your prescriber.

Even if NO to all of the above: You may still want to switch to transdermal given the safety advantages (particularly VTE risk). Discuss with your prescriber.

What to say: “I understand that transdermal HRT has a better safety profile than oral, particularly for VTE risk. I’d like to discuss switching from tablets to patches or gel.”

Most prescribers will support this — it aligns with current guidelines.

If Your Prescriber Resists Switching:

If your prescriber is reluctant to switch you from oral to transdermal:

Ask:

  • “Can you explain why you feel oral is more appropriate than transdermal in my case?”
  • “Are you aware of the current NICE guidelines recommending transdermal for women with risk factors?”
  • “What specific reason makes transdermal unsuitable for me?”

If the answer is vague (“oral is fine,” “you’re doing well on oral,” “no need to change”) rather than specific clinical reasoning:

Options:

  • Request second opinion from another GP in practice
  • Request referral to menopause specialist
  • Register complaint if care clearly falls short of guidelines
  • Seek private menopause specialist if financially possible

You have a right to evidence-based prescribing that aligns with current guidelines.

Special Situations

Can’t Tolerate Transdermal (Skin Reactions)?

If you’ve tried both patches AND gel and both cause unacceptable skin reactions:

Options:

  • Try different brands (adhesives and formulations vary)
  • Treat skin reactions (topical hydrocortisone under guidance)
  • If truly intolerable, oral may be necessary

In this case, oral HRT is better than no HRT (if you need symptom relief and have no contraindications).

However, if you have significant VTE or cardiovascular risk factors, the decision is more complex — discuss thoroughly with specialist.

Combined Patches (Oestrogen + Progestogen)

Combined patches are convenient but:

  • Progestogen is synthetic (not body-identical)
  • May have less favorable breast cancer risk profile than body-identical progesterone

Ideal for safety: Transdermal oestrogen patch/gel + separate oral micronized progesterone (Utrogestan)

But combined patches are still safer than combined oral tablets due to transdermal oestrogen route.

Testosterone

If you need testosterone (usually if ovaries removed or severe symptoms):

  • Testosterone for women is usually transdermal (gel)
  • Applied separately from oestrogen
  • Monitored with blood tests

Transdermal testosterone is absorbed well and appropriate doses are safe.

The Bottom Line

The route of HRT administration — oral vs. transdermal — is not a minor detail.

It fundamentally changes the safety profile, particularly for VTE (blood clot) risk, blood pressure, and cardiovascular effects.

The evidence is clear:

  • Oral oestrogen increases VTE risk 2-3 fold
  • Transdermal oestrogen does NOT increase VTE risk
  • Transdermal has better cardiovascular profile
  • Transdermal does not raise blood pressure

Current evidence-based guidelines recommend transdermal oestrogen as preferred — particularly for women with obesity, cardiovascular risk factors, VTE risk factors, over 60, or starting HRT >10 years post-menopause.

For many women, transdermal should be first-line.

If you’re on oral HRT and have any risk factors, discuss switching to transdermal with your prescriber.

If you’re starting HRT, request transdermal (patches or gel) rather than tablets unless there’s a specific reason why transdermal isn’t suitable.

This isn’t about being difficult or demanding. It’s about receiving evidence-based care that optimizes your safety while managing your symptoms.

Route matters. Ask about it. Advocate for transdermal if appropriate for you.

Need Support?

If you’re unsure whether you’re on the optimal HRT formulation or want to discuss switching from oral to transdermal, I can help.

As a registered nurse and prescriber specializing in menopause care, I provide evidence-based HRT prescribing aligned with current guidelines.

Book a consultation to review your HRT regimen and ensure it’s optimized for safety and effectiveness.

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