What are the various treatments for female hormone replacement therapy (HRT)?

From the Guidelines

Female hormone replacement therapy (HRT) should be individualized and used at the lowest effective dose for the shortest possible time, considering the patient's symptoms, risk factors, and treatment goals, as recommended by the most recent guidelines 1. The main types of HRT include:

• Estrogen-only therapy, typically prescribed for women who have had a hysterectomy, using medications like Premarin (conjugated estrogens) at 0.3-1.25mg daily or Estrace (estradiol) at 0.5-2mg daily
• Combined estrogen-progestogen therapy, recommended for women with an intact uterus to prevent endometrial cancer, with options like Prempro (conjugated estrogens/medroxyprogesterone) or separate estrogen with cyclic or continuous progestogen like medroxyprogesterone acetate (2.5-10mg daily) Alternative delivery methods include:
• Transdermal patches (Climara, Vivelle-Dot) applied once or twice weekly, delivering 0.025-0.1mg estradiol daily
• Vaginal preparations (creams, rings, tablets) for localized symptoms
• Bioidentical hormones that are chemically identical to those produced by the body It is essential to consider the patient's preference for route and method of administration, as well as contraceptive needs, when prescribing HRT 1. The treatment duration should be individualized based on symptom severity, risk factors, and treatment goals, with regular reassessment, and HRT should be used only for a limited period of time and at the lowest effective doses, especially in women with severe menopausal symptoms 1. HRT works by replacing declining hormone levels during menopause, alleviating symptoms like hot flashes, vaginal dryness, and mood changes, while potentially offering benefits for bone health and cardiovascular protection when started early in menopause. However, it is crucial to weigh the benefits and risks of HRT, considering the potential increased risk of breast cancer, cardiovascular, and thromboembolic morbidity, especially with prolonged use 1.

From the FDA Drug Label

INDICATIONS AND USAGE PREMARIN therapy is indicated in the: Treatment of moderate to severe vasomotor symptoms due to menopause. Treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered Treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure. Treatment of breast cancer (for palliation only) in appropriately selected women and men with metastatic disease. Treatment of advanced androgen-dependent carcinoma of the prostate (for palliation only). Prevention of postmenopausal osteoporosis When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medications should be carefully considered.

The various treatments for female hormone replacement include:

• Estrogen replacement therapy with conjugated estrogens (PO) or estradiol (PO) for the treatment of:
  • Moderate to severe vasomotor symptoms due to menopause
  • Moderate to severe symptoms of vulvar and vaginal atrophy due to menopause
  • Hypoestrogenism due to hypogonadism, castration, or primary ovarian failure
• Topical vaginal products for the treatment of symptoms of vulvar and vaginal atrophy
• Non-estrogen medications for the prevention of postmenopausal osteoporosis
• Calcium supplementation to ensure adequate daily intake in postmenopausal women
• Vitamin D supplementation to ensure adequate daily intake in postmenopausal women
• Weight-bearing exercise and adequate calcium and vitamin D intake as mainstays for decreasing the risk of postmenopausal osteoporosis 2, 2, 3

From the Research

Types of Hormone Replacement Therapy (HRT)

• Combined HRT: This type of therapy combines estrogen and progestogen to protect the endometrium against the proliferative effects of estrogens in postmenopausal women 4.
• Continuous combined HRT: This regimen involves taking estrogen and progestogen continuously, which has been shown to confer better protection against endometrial hyperplasia and cancer 4, 5.
• Low-dose HRT: This approach uses lower doses of estrogens and progestogens, which has been shown to be effective for treating vasomotor symptoms and preventing bone loss, while also reducing side effects 5, 6.
• Sequential HRT: This regimen involves taking estrogen and progestogen in a sequential manner, which can protect the endometrium if exposure to progestogen lasts for at least 12 days/month 7.

Progestogens Used in HRT

• Micronized progesterone: This progestogen has been shown to have a more favorable effect on breast tissue compared to synthetic medroxyprogesterone acetate (MPA) 4.
• Medroxyprogesterone acetate (MPA): This progestogen has been shown to increase cell proliferation in breast tissue, which may increase the risk of breast cancer 4.
• Dydrogesterone: This progestogen may be safer in terms of breast cancer risk compared to other progestogens 7.
• Levonorgestrel: This progestogen can be given through the intrauterine route and may be safer in terms of breast cancer risk compared to other progestogens 7.

Routes of Administration

• Oral: Estrogen and progestogen can be taken orally, which is a common route of administration for HRT 5, 6, 8.
• Transdermal: Estrogen can be applied transdermally, which may be a suitable option for women who experience side effects with oral HRT 6.
• Vaginal: Progestogen can be given vaginally, which may be a suitable option for women who experience side effects with oral HRT 7.
• Intrauterine: Levonorgestrel can be given through the intrauterine route, which may be a suitable option for women who experience side effects with oral HRT 7.