Category:Hormone replacement therapy

Hormone replacement therapy (HRT) is the administration of an exogenous hormone to replace a deficient endogenous hormone, restoring physiological or near-physiological hormone concentrations. The category covers postmenopausal estrogen-progestin replacement (the most common clinical use of the term and the principal subject of this page), testosterone replacement in male hypogonadism, growth-hormone replacement in childhood and selected adult deficiency, glucocorticoid and mineralocorticoid replacement in adrenal insufficiency, thyroid-hormone replacement in hypothyroidism, vasopressin replacement in central diabetes insipidus, and gonadotropin and gonadal-steroid replacement in disorders of the hypothalamic-pituitary-gonadal axis.

The dominant clinical conversation about HRT concerns the postmenopausal estrogen-and-progestin combination, used to treat menopausal vasomotor symptoms (hot flashes, night sweats), genitourinary syndrome of menopause (vaginal dryness, dyspareunia, urinary urgency), and (historically) to prevent osteoporotic fracture and cardiovascular disease. The pharmacological history is told under sex hormones: the 1923 Allen-Doisy estrogen-bioassay paper, the 1929 isolation of estrone, the 1942 introduction of conjugated equine estrogens (Premarin, Ayerst), the 1960 introduction of the first combined oral contraceptive, and the gradual extension of post-menopausal HRT through the 1960s and 1970s as a widely-prescribed treatment for menopausal symptoms and as a presumed cardiovascular-preventive medicine on the basis of observational studies (the Nurses' Health Study and others).

The 2002 publication of the Women's Health Initiative (WHI) trial reframed the entire field. The WHI was a National Institutes of Health-funded randomised controlled trial of combined conjugated equine estrogens plus medroxyprogesterone acetate (Prempro) versus placebo in 16,608 postmenopausal women aged 50 to 79 with intact uterus. The trial was stopped at 5.2 years of mean follow-up because the active arm showed increased rates of breast cancer (HR 1.26), coronary heart disease (HR 1.29 in early analyses, attenuated in subsequent reanalyses), stroke (HR 1.41), and venous thromboembolism (HR 2.11), partially offset by reductions in colorectal cancer and hip fracture.^[1] The parallel estrogen-only arm in women with prior hysterectomy showed no overall benefit on cardiovascular events but did show an increase in stroke; that arm was stopped in 2004.

The WHI fundamentally reshaped clinical practice. HRT prescribing in the United States fell by approximately 70 percent in the two years after the 2002 announcement. The subsequent reanalyses (the "timing hypothesis" that early HRT in the 50-59 age group has more favourable cardiovascular profile than HRT initiated in older women; the recognition that the conjugated equine estrogens and oral medroxyprogesterone of the WHI may produce greater risk than other estrogen formulations and progestin choices; the parsing of the early-onset vs late-initiation effects in the ELITE and KEEPS trials) have substantially refined but not reversed the WHI conclusions. The contemporary clinical recommendation, codified in the 2022 NAMS position statement and the 2023 endocrine society guidelines, is that HRT is appropriate for symptomatic menopausal women under age 60 or within 10 years of menopause onset, at the lowest effective dose, for the shortest duration consistent with symptom control, with transdermal estradiol preferred over oral conjugated equine estrogens (lower VTE risk), and with micronised progesterone preferred over medroxyprogesterone (lower breast-cancer signal in observational data). Vaginal estrogen for genitourinary syndrome of menopause is not subject to the same systemic-HRT risks and is offered more freely.

The other major HRT indications have less controversial histories. Thyroid-hormone replacement with levothyroxine (synthetic T4, brand-name Synthroid, available since 1955) is the standard treatment of hypothyroidism and is among the most-prescribed medicines in primary care worldwide; the issues are dose-titration, brand-name versus generic-substitution stability, and the question of whether to add liothyronine (T3) for patients with persistent symptoms despite biochemical euthyroidism on levothyroxine alone. Testosterone replacement in male hypogonadism (the contemporary formulations include the testosterone topical gels Androgel and Testim, the long-acting injectable testosterone enanthate and cypionate and undecanoate, the testosterone undecanoate oral Jatenzo, the testosterone-pellet Testopel, the testosterone nasal Natesto, and the testosterone transbuccal Striant) has substantial controversy of its own (the TRAVERSE 2023 trial established cardiovascular non-inferiority for testosterone gel in hypogonadal men with cardiovascular risk factors, partly answering a long-standing concern). Growth-hormone replacement in childhood deficiency (the recombinant human growth hormone, Protropin / Humatrope / Norditropin / Genotropin / Saizen, since 1985) has progressively expanded its indication set (Turner syndrome, idiopathic short stature, Prader-Willi, chronic kidney disease in childhood, adult growth-hormone deficiency). Glucocorticoid and mineralocorticoid replacement in adrenal insufficiency (hydrocortisone or prednisone for glucocorticoid; fludrocortisone for mineralocorticoid) is described under corticosteroids; the dose is physiological-replacement rather than pharmacological. Vasopressin replacement (desmopressin nasal, oral, or subcutaneous) in central diabetes insipidus is described under hormones.

By replaced hormone:

• Estrogen-progestin (postmenopausal HRT):
  • Estrogens: estradiol (oral, transdermal patch, transdermal spray, vaginal ring); conjugated equine estrogens (Premarin); ethinylestradiol (more often used in hormonal contraceptives); estradiol valerate
  • Progestins (added in women with intact uterus to prevent endometrial hyperplasia): micronised progesterone (Prometrium); medroxyprogesterone acetate (Provera); norethindrone acetate; levonorgestrel intrauterine system (Mirena, used as the progestin component of HRT in selected patients)
  • Fixed combinations: Prempro (CEE + medroxyprogesterone), Activella (estradiol + norethindrone), Climara Pro (transdermal estradiol + levonorgestrel), Bijuva (estradiol + progesterone, the first bioidentical fixed combination)
  • Tibolone (Livial, Europe; synthetic steroid with estrogen, progestin, and androgen activity)
• Vaginal estrogen (for genitourinary syndrome of menopause):
  • Vaginal estradiol tablets (Vagifem), cream (Estrace), ring (Estring), and softgel inserts (Imvexxy)
  • Vaginal estriol (Europe)
  • DHEA vaginal suppository (Intrarosa)
• Estrogen + bazedoxifene (TSEC, tissue-selective estrogen complex):
  • Duavee (conjugated estrogens + bazedoxifene; for women with intact uterus, no progestin needed)
• Testosterone replacement (male hypogonadism):
  • Topical: Androgel, Testim, Axiron, Fortesta
  • Injectable: testosterone enanthate, testosterone cypionate, testosterone undecanoate
  • Oral: testosterone undecanoate (Jatenzo)
  • Buccal: Striant
  • Nasal: Natesto
  • Pellet: Testopel
• Thyroid-hormone replacement:
  • Levothyroxine (Synthroid, Levoxyl, Tirosint; the standard)
  • Liothyronine (Cytomel; selected use)
  • Desiccated thyroid extract (Armour Thyroid, Nature-Throid; traditional)
• Growth-hormone replacement:
  • Daily recombinant human growth hormone: Humatrope, Norditropin, Genotropin, Saizen, Omnitrope, Nutropin
  • Long-acting weekly: somatrogon (Ngenla), somapacitan (Sogroya), lonapegsomatropin (Skytrofa)
• Adrenal hormone replacement (cross-indexed under corticosteroids):
  • Hydrocortisone (the foundation), prednisone, dexamethasone for selected indications
  • Fludrocortisone (for mineralocorticoid replacement)
• Vasopressin replacement:
  • Desmopressin (nasal, oral, subcutaneous; central diabetes insipidus, nocturnal polyuria, von Willebrand disease)
• Gonadotropin replacement:
  • Recombinant human chorionic gonadotropin, recombinant follicle-stimulating hormone, menotropins (for fertility induction)

The boundary of this category is "medicine administered to replace a deficient endogenous hormone." The supraphysiological pharmacological-dose use of hormones (high-dose glucocorticoid anti-inflammatory therapy, pharmacological-dose vasopressin in shock, the high-dose contraceptive doses of combined oral contraceptive in non-replacement indications) is conceptually distinct from replacement therapy and is listed under the appropriate primary class. The closely related gender-affirming hormone therapy for transgender adults (testosterone in masculinising therapy; estradiol and antiandrogen in feminising therapy) is mechanistically the same as the replacement therapy of opposite-sex hypogonadism and is conventionally listed alongside HRT in the contemporary endocrine literature; the regulatory positioning of these medicines reflects clinical equivalence to other hormone-replacement use. The medicines used in hormonal contraceptives use the same chemistry as HRT but at supraphysiological doses and for a different indication; they are listed separately.

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.