What is the proper administration of transdermal Hormone Replacement Therapy (HRT)?

From the Guidelines

Transdermal hormone replacement therapy (HRT) should be used with the lowest effective dose for the shortest possible time, as recommended by the most recent guidelines 1. To use transdermal HRT, clean and dry the application area first, typically the lower abdomen, upper thighs, or buttocks for patches, and inner arms, shoulders, or thighs for gels and sprays.

Key Considerations

• For patches like Estradot or Climara, apply a new patch once or twice weekly according to your prescription, rotating sites to prevent skin irritation.
• For gels like Estrogel or Divigel, apply the prescribed amount (usually 1-2 pumps) to clean skin once daily, allowing it to dry before dressing.
• Spray forms like Evamist require 1-3 sprays to the inner forearm daily.
• Apply at approximately the same time each day to maintain consistent hormone levels.

Progesterone Regimens

If using progesterone alongside estrogen (necessary if you have a uterus), follow your specific regimen, which may include oral progesterone or combination patches.

• Medroxyprogesterone acetate (MPA) is a commonly used progestin, but natural micronized progesterone (MP) has a more favorable safety profile 1.
• The dose of progestogen is based on the concurrent dose of estrogen administered, and clinicians should choose between a sequential and continuous regimen of administration 1.

Administration and Monitoring

Transdermal delivery bypasses the liver's first-pass metabolism, allowing for lower doses and potentially fewer side effects than oral forms while providing steady hormone levels throughout the day.

• Wash hands after application to avoid transferring hormones to others, and follow your healthcare provider's specific instructions regarding your individual HRT regimen.
• Regular monitoring of hormone levels, blood pressure, and other health parameters is essential to ensure the safe and effective use of transdermal HRT 1.

From the FDA Drug Label

When estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be initiated to reduce the risk of endometrial cancer. A woman without a uterus does not need progestin Use of estrogen, alone or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. For treatment of moderate to severe vasomotor symptoms, vulval and vaginal atrophy associated with the menopause, the lowest dose and regimen that will control symptoms should be chosen and medication should be discontinued as promptly as possible. The usual initial dosage range is 1 to 2 mg daily of estradiol adjusted as necessary to control presenting symptoms. Administration should be cyclic (e.g., 3 weeks on and 1 week off).

To use transdermal HRT (Hormone Replacement Therapy), specifically estradiol (TD), the following steps should be taken:

• Start with the lowest dose (1 to 2 mg daily) and adjust as necessary to control symptoms.
• Use the medication for the shortest duration consistent with treatment goals and risks.
• Administer the medication in a cyclic regimen (e.g., 3 weeks on and 1 week off).
• For women with a uterus, a progestin should also be initiated to reduce the risk of endometrial cancer.
• Reevaluate patients periodically (e.g., every 3 to 6 months) to determine if treatment is still necessary 2.

From the Research

Transdermal HRT Usage

• Transdermal estrogen therapy is effective for treating vasomotor symptoms of menopause and does not increase the risk of venous thromboembolism (VTE) in healthy postmenopausal women 3
• In women at increased risk for VTE, such as those with prior VTE, increased body mass index, thrombophilia, or proinflammatory comorbidities, transdermal MHT use has been found to have a minimal to no increased VTE risk 3
• The addition of progestogens to estrogen therapy helps reduce the risk of endometrial hyperplasia and improves adherence to therapy 4, 5, 6
• Progesterone and progestins are likely equally effective in preventing endometrial hyperplasia/cancer when used at adequate doses 7

Administration and Regimens

• A cyclic combined regimen comprising estrogen and 100 mg micronized progesterone administered on days 1-25 has been shown to provide endometrial safety, absence of bleeding, and a high rate of tolerability 5
• Continuous combined therapy may be more effective than sequential therapy in reducing the risk of endometrial hyperplasia at longer durations of treatment 4, 6
• Monthly sequential therapy (progestogen given every month) may be more effective than long cycle sequential therapy (progestogen given every 3 months) in preventing endometrial hyperplasia 4, 6

Safety and Efficacy

• Menopausal hormone therapy containing estradiol (E2) versus other estrogens and progesterone (P4) versus progestins may have a differential effect on safety profiles, with some evidence trending towards a potentially better safety profile with E2 and/or P4 7
• Transdermal MHT use in postmenopausal women at increased risk of VTE has been found to have a minimal to no increased VTE risk, and clinicians should have risk versus benefit discussions with each patient regarding its use 3