Hormone Replacement Therapy (HRT) Initiation and Monitoring

Indications for HRT

The American College of Obstetricians and Gynecologists and other guideline societies recommend HRT for treatment of estrogen deficiency symptoms in women with premature ovarian insufficiency (POI) and for relief of bothersome menopausal symptoms in postmenopausal women, but should not be initiated for primary or secondary prevention of cardiovascular disease 1, 2
HRT effectively treats vasomotor symptoms, genitourinary syndrome of menopause, and provides bone protection in women with POI 1, 3
Women with POI should be informed that HRT may have a role in primary prevention of cardiovascular disease and bone protection, with a different risk-benefit profile than HRT in naturally menopausal women 1, 3

Before initiating HRT, evaluate cardiovascular risk factors, including history of coronary heart disease, stroke, hypertension, diabetes, and hypercholesterolemia 4
Assess thrombotic risk, including personal or family history of venous thromboembolism 5
Evaluate breast cancer risk, including personal or family history and BRCA mutations 1, 2
Assess endometrial cancer risk, including uterine status (intact vs hysterectomy) 1, 5

The Endocrine Society recommends 17β-estradiol administered transdermally as the preferred first-line approach, particularly for women with cardiovascular risk factors or hypertension 1, 6
Transdermal 17β-estradiol avoids hepatic first-pass metabolism, reducing impact on coagulation factors and is preferred in women with hypertension 6, 1
The standard adult dose is 50-100 mcg/day transdermally, which may be increased to 200 mcg/day if needed 1, 6

All women with an intact uterus must receive progestogen in combination with estrogen to protect the endometrium, according to the American College of Obstetricians and Gynecologists 1, 6
Micronized progesterone (MP) 100-200 mg orally daily for 12-14 days every 28 days is the first choice for progestogen therapy 6

Hypertension is not a contraindication to HRT in women with POI, and transdermal estradiol is the preferred delivery method 1
Migraine is not a contraindication to HRT in women with POI, but consider changing dose, route, or regimen if migraine worsens during HRT 1
HRT is a treatment option for women with BRCA1/2 mutations without personal history of breast cancer after prophylactic bilateral salpingo-oophorectomy 1

Once established on therapy, women with POI using HRT should have a clinical review annually, with particular attention to compliance, according to the Endocrine Society 1, 3
Annual review should include assessment of symptom control, treatment satisfaction, and evaluation of compliance with prescribed regimen 1, 3

The North American Menopause Society recommends discussing the risks and benefits of HRT with patients, including the risk of breast cancer, cardiovascular disease, and thromboembolism 1, 5
HRT has not been found to increase breast cancer risk before the age of natural menopause, but may provide protective benefits against cardiovascular disease in this population 1, 3
Naturally menopausal women using HRT have a small increased risk of breast cancer, stroke, and venous thromboembolism, but also have a reduced risk of hip fractures and colorectal cancer 5, 2