Is transdermal estrogen and progesterone (hormone replacement therapy) required for a patient with an intact uterus?

From the Guidelines

Transdermal Estrogen and Progesterone Therapy

For individuals with an intact uterus, transdermal estrogen therapy requires concurrent progesterone administration to mitigate the risk of endometrial hyperplasia and cancer, as emphasized by studies such as 1 and 1.

• A typical regimen consists of transdermal estradiol (0.025-0.1mg/day) combined with oral micronized progesterone (100-200mg/day) or medroxyprogesterone acetate (2.5-5mg/day) for a minimum of 12-14 days per month.
• Alternatively, a continuous combined regimen of transdermal estradiol (0.025-0.1mg/day) and oral micronized progesterone (100-200mg/day) or medroxyprogesterone acetate (2.5-5mg/day) can be used, with treatment duration individualized based on symptom management and patient needs, as supported by 1.

Key Considerations

• Progesterone is essential to protect the endometrium in women with an intact uterus, as highlighted in 1.
• The choice of estrogen delivery method, such as transdermal estradiol, may depend on individual patient factors, including hypertension, as noted in 1.
• Regular monitoring and assessment of patient needs and symptoms are crucial in managing hormone replacement therapy, as implied by the guidelines in 1 and 1.

From the FDA Drug Label

PATIENT INFORMATION Progesterone Capsules, 100 mg and 200 mg Rx only Protection of the Endometrium (Lining of the Uterus) Progesterone capsules are used in combination with estrogen-containing medications in a postmenopausal woman with a uterus (womb). Taking estrogen-alone increases the chance of developing a condition called endometrial hyperplasia that may lead to cancer of the lining of the uterus (womb) The addition of a progestin is generally recommended for a woman with a uterus to reduce the chance of getting cancer of the uterus (womb).

Hormone Replacement Therapy (HRT) Requirements

• For a patient with an intact uterus, transdermal estrogen and progesterone (hormone replacement therapy) is required to reduce the risk of endometrial hyperplasia and cancer.
• The combination of estrogen and progesterone is generally recommended for women with a uterus to provide protection against endometrial hyperplasia and cancer 2, 2.

From the Research

Hormone Replacement Therapy for Postmenopausal Women with an Intact Uterus

• Transdermal estrogen and progesterone (hormone replacement therapy) is required for a patient with an intact uterus to protect the endometrium against the proliferative effects of estrogens 3, 4, 5.
• The protective effect of progestogens against hyperplasia and endometrial cancer does not appear to differ with different progestogens, but appears to be affected by the regimen and thus the dose, with continuous combined treatment conferring better protection 3.
• Micronized progesterone may be the optimal choice as part of combined HRT for women with an intact uterus, as it does not increase cell proliferation in breast tissue in postmenopausal women compared with synthetic medroxyprogesterone acetate (MPA) 3.
• Continuous combined transdermal HRT with estrogen and progestogen shows no evidence of an increased endometrial hyperplasia or endometrial cancer risk over a 96-week period 4.
• Hormone therapy for postmenopausal women with an intact uterus should comprise both estrogen and progestogen to reduce the risk of endometrial hyperplasia 5.

Types of Progestogens and Their Effects

• Micronized progesterone and progestogens are recommended as part of combined HRT in women with an intact uterus 3.
• Oral micronized progesterone provides endometrial protection if applied sequentially for 12-14 days/month at 200 mg/day for up to 5 years 6.
• Vaginal micronized progesterone may provide endometrial protection if applied sequentially for at least 10 days/month at 4% (45 mg/day) or every other day at 100 mg/day for up to 3-5 years (off-label use) 6.
• Transdermal micronized progesterone does not provide endometrial protection 6.

Treatment Regimens and Their Effects

• Continuous and cyclical transdermal estrogen replacement therapy (ERT) reduced climacteric symptoms in postmenopausal women, with or without an oral progestogen 7.
• The addition of an oral progestogen did not influence the effect of ERT on body weight or bleeding pattern in patients with an intact uterus 7.