HRT Flashcards
(11 cards)
1
Q
Menopause
A
- Ovaries secrete significantly less E — FSH and LH increase
- Uterine bleeding stops
- Mean age = 51
S/sx
- HOT FLASHES
- night sweats
- mood swings
- INSOMNIA
- wt gain, decreased metabolism
- thinning hair, dry skin
- vaginal dryness
- bone loss
2
Q
HRT
A
Human estrogens
- Estradiol
- Estrone
- Estriol
Synthetic estrogens
- Ethinyl estradiol
- Mestranol
- Conjugated estrogens
- Diethylstilbestrol
Phytoestrogens
- Soy
- Red cover
- Flax
- Alfalfa
- Black cohosh
- Dong quai
3
Q
Estrogen/Progestrone
A
Oral estrogen
- Conjugated estrogens (Premarin, Cenestin, Enjuvia)
- Esterified estrogens (Menset)
- Estropipate (Ogen, Ortho-Est
- Micronized estradiol (Estrace)
Progestogen
- Dydrogesterone
- Medroxyprogesterone acetate
- Micronized progesterone
- Norethindrone
- Norgestrel
- Levonorgestrel
Topical estrogen
- Estradiol patch (Alora, Climara, Vivelle)
- Estradiol emulsion (Estrasorb)
- Estradiol gel (Elestrin, Esrogel, Divigel)
- Estradiol spray (Evamist)
Vaginal estrogens/?????
4
Q
Oral estrogen
A
Conjugated equine estrogens (CEE)
- estrone sulfate and equine estrogens
Esterified estrogens: estrogen mixture
Estradiol
- Micronized to small particles for better absorption
- Liver metabolism partly via CYP 3A4 (converted to estrone which is less potent)
- Ethinyl estradiol (synthetic with similar activity)
5
Q
Estrogen
Indications: relief of vasomotor sx
A
ADR
- N, HA, breast tenderness, bleeding
- Serious: CHD, CVA, VTE, breast cancer, gallbladder dz
- Less likely with transdermal estrogens
WARNING (increases with age)
- Increased risk of stroke
- VTE: d/c estrogens at least 4-6 wks before surgery with an increased risk of thromboembolism or during periods of prolonged immobilization
- Endometrial cancer: no unopposed estrogen in a woman with a uterus!!!!!!—- monitor estrogen users closely; w/u including endometrial biopsy to r/o malignancy in postmenopausal women with undiagnosed persistent or reccuring abnormal genital bleeding; no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose; adding a progestin to postmenopausal estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer
- Breast cancer: risk increased with duration of use and returned to baseline over 5 yrs after stopping tx; observational studies suggest risk of breast cancer was greater, and became apparent earlier (3-5 yrs of tx), with estrogen plus progestin therapy as compared to estrogen-alone therapy; the use of estrogen-alone and estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation
- Dementia
- Coronary heart dz
- Gels, sprays, emulsions have variable absorption
- No first-pass effect
- Levels closer to pre-menopausal state (Estradiol > estrone)
- Less change in lipids, SHBG
- Skin rxn with patches
- Intravaginal forms generally used for vaginal atrophy
- Can have systemic effect (dose less frequently than orals to keep systemic levels lower)
- Lower estrogen absorption with tablets and rings than creams
- Rings (sustained release estradiol in liquid polymer matrix)
6
Q
HRT: estrogen + progesterone
A
—study: stopped early due to increased risk of CHD, CVA, PEs, invasive breast cancer
7
Q
estrogen only vs estrogen + progesterone
A
Estrogen alone: higher stroke risk
Estrogen + progesterone: higher invasive breast cancer and dementia risk
- No protective effects of HRT on all-cause mortality, CV death or MI
- Increased risk of DVT and PE
- Increased risk of CVA
8
Q
Phytoestrogens
Isoflavones: soy, garbanzos, red clover, lentils, beans
Lignans: flaxseed, low amounts in fruits, lentils, whole grains, beans, veggies
Coumestens: red cover, sunflower seeds, sprouts
A
- Not structurally related to estrogen
- Contain a phenolic ring that allows them to bind to estrogen receptors
- A LOOOOOT weaker than endogenous estrogen
- Can act as estrogens (in post menopausal) OR antiestrogens (in premenopausal)
- Act similar to SERMs
Risk
- increase proliferation of breast tissue in vitro
- may decrease risk of breast cancer in asian women (western women evidence)
- best advice: women with breast cancer, h/o breast cancer, or FH should avoid phytoestrogens; food probably ok, but avoid supplement
For Hot flashes
- Soy extracts
- Red clover: ineffective for hot flashes, may increase bleeding with warfarin
- Flaxseed: in place of other dietary fats significantly improves MILD menopausal sx (high in calories)
- Black cohosh: does NOT directly bind E receptor, up-regulate E-dependent genes or stimulate the growth of E-dependent tumor; may be serotonin agonist– mood stabilizer?; it appears to increase markers of bone formation; may have SERM-like activity; monitor liver fxn
Avoid dong quai: carcinogenic potential
Avoid chasteberry: no evidence of efficacy, may stimulate breast tissue hyperplasia
- No evidence for ginseng, kudzu, alfalfa, hops, licorice
9
Q
Wild Yam
A
- Use root and rhizome
- Diosgenin: used to produce steroidal components; not bioavailable to humans in natural state
- Natural alternative for HRT, PMS, infertility, menstrual disorders
- Topical use no better than placebo for hot flashes and night sweats (no changes in FSH, estradiol or progesterone levels)
- ADRs: orally, large doses cause V
10
Q
Flibanserin (AddyI)
Indication: premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD)
A
- low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to: coexisting medical or psych condition, relationship issues, not for enhancement of sexual performance
- CI: EtOH, P450 3A4 inhibitors, hepatic impairment
- MOA: unknown (5HT receptor agonist at 5HT1A, 5HT receptor antagonist at 5HT2A-C and dopamine D4 receptors)
- DI: EtOH, P450 3A4 inhibitors
- Genomics??????
- ADR???????
11
Q
Guidelines
GO THROUGH GUIDELINE AGAIN
A
- Lowest dose for shortest duration
- Benefits outweigh risks for women < 60 yo
- Estrogen most effective treatment: vasomotor sx (sleep, irritability, concentration, reduced QOL); vulvular and vaginal atrophy (vaginal dryness, dyspareunia, atrophic vaginitis)
- Reduces post menopausal fractures
- Local estrogen may help with OAB, vaginal dryness/atrophy
……???????
