• ERT – Estrogen replacement therapy (unopposed estrogen therapy)
• Synonyms: ET - estrogen therapy, PET - postmenopausal estrogen therapy
• HRT – Hormone replacement therapy (combinations and permutations of estrogen and progestin)
• Synonyms: HAT - hormone additive therapy, EPT - estrogen-progestin therapy
• LTHRT – Long-term hormone replacement therapy
• Progestin – sex steroid with progesterone-like activity

Rationale behind HRT – three effects:

• (1) Ý gonadotropin levels, ß sex steroid and inhibin levels
• (2) Direct positive effects on musculoskeletal, cardiovascular, and CNS
• (3) Prevention of osteoporotic fractures and CHD

• Currently available drugs
• Estrogen: estrone(E₁), 17b estradiol(E₂), estriol(E₃), conjugated equine estrogens(from pregnant mare's urine)
• E₁ and E₂ are predominately in clinical use
• Progestins:
• C-19 progestins: estranes, gonanes
• Synthetic derivatives of 19-nortestosterone, have some degree of androgenic activity
• C-21 progestins: pregnanes
• Synthetic derivatives of 17a -acetoxyprogesterone, structurally related to progesterone
• Natural progesterone
• Now available in orally absorbable micronized form
• SERMS (Selective Estrogen Receptor Modulators) – tissue selective estrogens
• Tamoxifen – selective anti-estrogenic effects on breast, pro-estrogenic effects on bone and endometrium
• Raloxifene – 2^nd generation SERM, anti-estrogenic effects on breast and uterus and pro-estrogenic effects on bone and possibly cardiovascular system.
• Routes of Administration
• Transdermal patches (estrogen, estrogen and progestin, or testosterone) allow bypass of "first pass" effect thus reducing deleterious effects on liver (Ý blood clotting factors, Ý angiotensin, Ý LDL, etc.)
• vaginal rings
• vaginal creams
• transdermal creams
• injectables
• implants
• Regimens - currently two popularly utilized regimens
• (1) Continuous estrogen and intermittent progestin–daily estrogen with progestin on days 1-12 of each/alternate month
• (2) Combined continuous – estrogen and progestin continuously
• Risks – Ý endometrial cancer (unopposed estradiol usage), Ý breast cancer, Ý venous thromboembolism, Ý cardiovascular disease, mastodynia (breast pain), bleeding
• Benefits – Relief of vasomotor symptoms and UG atrophy, ß bone resportion, ß osteoporotic fractures, ß cardiovascular disease, positive impact on sexuality, Ý cognitive function, maintenance of skin collagen matrix, ß gingival disease, ß dental caries, ß risk of colon cancer

• ß hot flashes, ß vaginal dryness, ß fractures, ß heart attack, mood elevation, ß Alzheimer's disease, no Ý in breast cancer.
• Polls indicate:
• the top reason women start HRT is to relieve hot flashes
• the top reason women refuse HRT is concern about cancer

• Lower doses
• non-hormonal alternates
• tissue selective estrogens (SERM)
• starting HRT even in older patients
• HRT following treated breast cancer (currently HRT is not given to patients who had breast cancer, except for those experiencing severe symptoms)