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PRE-CLASS QUIZ REVIEW
kava "druglike" for shorter term use, acute muscle pain, anxiety
volatile oils directly affect limbic system
hallucinogenic: tropane alkaloids

REPRODUCTIVE HORMONES CTD: Menopause and more

MENOPAUSE

HORMONE REPLACEMENT
controversial tx
pros of hormone replacement: alleviate sx, may help prevent osteoporosis, Alzheimers
cons: may increase risk of CAD, stroke, clots, CA, gallstones
heart dz and birth clots on BC pills esp in smokers

BONE
est replacement and bone density: Stansbury not convinced that results are impressive
does somewhat increase thickness of cortical bone
may damage trabecular/spongy bone, highly vascular area

PREMPRO vs HRT est vs placebo study by WHI n=16000
use of HRT was discontinued 5 years into study
it appeared to incr risk of breast CA and CV dz
7-8 of EACH PER 1000 women per year

PROGESTERONE ONLY therapy
oral prog and prog cream are popular
however like est, prog should not be used in pts with hormone sensitive CA
constant stim of breasts with any hormones seems to incr CA

POMEGRANATE
prob will be part of herbal replacement therapy someday
contains ESTRONE
rare that plants contain animal steroids
symbol of fertility, persephone who lived underground
mother Demeter goddess of grains
mother-daughter visits-->world becomes summer
(other plant sources: mushrooms--ergosteraol, hops and dates--estradiol)

PHYTOSTEROL VS PHYTOESTROGEN
true steroid vs compound with hormonal effects
sterol has true steroidal nucleus

phytoestrogen has some effect but is not steroid
phytoest: antibx, plant compounds incl isoflavones in soy, pesticides,
herbicides bind est receptor (agonists),
some herbs impact dopamine & serotonin later effect FSH and LH, prolactin, TSH
"estrogenic"

MENOPAUSE THERAPY
plant compounds: phytosterols can bind est receptors and prog receptors, agonist
gonadotropins: fsh, lh, vitex, cimicifuga, wonderful for menopause dt dopaminergic action
enzyme affectors: aromatase enzyme found in peripheral lipid cells under skin
aromatase converts prog and test to est
aromatase inhibitors valuable: lower est for fibrocystic breast, uterine polyps, endometriosis, prost, breast, endometrial CA tx, lower proliferation dt est stimulation
arimidex for breast ca to decr est load
named thusly because is aromatase inhibitor

estrogen agonists and estrogen receptor activity:
steroidal receptors usu intracellular
est receptors can be bound by many things besides est, not esp picky
benzene like ring may bind, solvents, pesticides, ABX all agonists
endocrine dysrupters
mutations in amphibians in polluted water, two headed frogs, loss of one gender (which?)
hemaphroditism
1000 drug residues in tap water
in humans even in utero: may reg genes differently
gene expression research

amphoteric means goes action can go either way

plant est agonists: coumestins, isoflavones, etc bind est receptors usu as agonists
weaker than body's endogenous est (all 3 types)
so can decrease estrogen action by crowding out estradiol
plant est 1/6-1/20 as strong an estrogen
decr est load
for breast cysts, PMS, endometriosis

opposite
post-menopausal woman or surgical menopause (total hysterectomy)
no est in body or very little
add some from plants: increases est activity in body


UTERINE TONICS
FOR: DUB, prolapse, fibroids, endometriosis
viburnum
angelica
tone muscle
fibroids can grow quickly during perimenopause
normal for prog to drop before est in peri
many women get more PMS and breast cysts in peri

VASCULAR TONICS
medical community backpedaling on claim that HRT prevents vasc probs
claimed est was protective

NERVINES
for menopause, PMS, mood swings, insomnia
calm, relax

PHYTOSTEROLS
white powders with mild, characteristic odor
insoluble in water and soluble in alcohols
used to lower total cholesterol: blocks intestinal absorption
added to margarine/butter, breakfast cereals, marketed at pts w/ high chol

MAIN TYPES OF PHYTOSTEROLS
ISOFLAVONES in soy bind steroidal receptors
COUMESTANS particularly in legumes same as one above
but all research on soy
licorice has coumestans (tis a legume!)
red clover (trofolium)
metacago (alfalfa) very nutritious
prob all bone building, alfalfa also has minerals
STEROIDAL SAPONINS found dotted about
mushrooms, licorice, bupleurum
saponins have full steroidal nucleus plus one more ring
LIGNANS not exactly phytosterol more like cellulose
intestinal bacteria turn them into steroids
enterolactone, enterodiol is estradiol like made in intestines
must have healthy intestinal ecosystem
women who are constipated are more likely to have hormonal related CA, breast CA
good enterodiol production helps with est overload ??

ISOFLAVONES
genistein: most researched
daidzein
biochanin
formononetin
pratensin
for bone density, vasc health, other, chol, endometrium, prost, decr alzheim
exist free as phenolics and bound to sugar as glycosides
weakly estrogenic and receptor selective
plants: glycine max (soy), trifolium praetense and glycyrrhiza

EQUOL
isoflavones esp dadzein may be metabolized by gut bact into equol
a nonsteroidal estrogen agonist
S-Equol preferentially activates estrogen receptor type β
also DHT blocker
about 30-50% of people have intestinal bacteria that make equol
may prevent prostate cancer
may help with menopause sx
also used for: male pattern baldness, acne

new findings: many plant compounds are agonist in some tissue and antagonist in other tissues
good for targeting tx
SERM = selective estrogen response modifier
search for pharmaceuticals to do this but we already have botanicals that do it

COUMESTANS
the most active phytosterols
not as readily available in diet
coumesterol is most studied
medicago, trifolium, taraxicum
trigonella conriculata is fenugreek also for blood sugar and lactation

STEROIDAL SAPONINS
beta sitosterol
widely distributed in plants esp. nuts, seeds, legumes
diosgenin in dioscorrea, smilax, daucus carrota, aletris farinosa, chamelerium luteum
many of these not used in allo tx
one of the original mols used to make BC pills
diosgenin used as raw material-->estradiol
stigmasterol in soy, licorice, alfalfa, sage (dopaminergic), fennel
other saponins in ginseng
daucus carrota = queen anne's lace
**foeniculum vulgare = fennel for colic, promote lactation in nursing women (galactogogue)
(salvia = sage is excellent anti-galactogogue)
chamelirium sweet little plant
smilax not so common in products, root beer like tea, this vine looks very familiar
many slides of different smilax spp.
mitchella repes = partidge berry for chronic miscarriage or infertility, improve uterine tone
panax ginseng = antiaging, energy, sexual fx in older years, viagra of ancient times
taraxicum officinale
medicago nourishing good in tea

LIGNANS
fiber like, gummy or fibrous parts
metabolized into enterodiol and enterolactone by GI bact
estrogenic
sources: flax, wheat, oats, rye, legumes, soy

linum ussitatissimum = flax
flax seeds, used to filter out lignans from oil, then research said it's good

glycine max = soy
weak estrogenic effect
for hot flashes and bone density
may depress thyroid fx, is this the processed kinds or only in pts with low iodine?
104 postmenopausal women eating 60gm/day soy vs placebo: less hot flashes with soy
heart: reduces LDL by 10%, reduce total chol by 13%, not affect HDL
isoflavones don't alleviate hot flashes when purified: need whole plant parts
what about breast CA? soy being weak estrogenic agent appears to decr CA
80% of studies say decrease, 20% say they stim CA

phytoestrogens may interfere with tamoxifen, could increase hormonal load, complicated
very low doses (under 10 micromols/liter) stim breast tumor sby blocking inhibit of tamox
higher doses inhibit breast turmor growth and enhance tamoxifen action
dangerous: bombard person with CA hx with lots of phytoestrogens
one study compared phytoest with placebo for effect in uterine lining
found no sig endometrial prolif in tx group

cimicifuga racemosa = black cohosh
generate FSH and LH
weak est agonist
dopaminergic-->prolactin antagonist

trifolium pratense = red clover
farmers with large pastures of clover many grazing animals may develo hormonal disorder
males low sperm counts
females uterine fibroids and pregnancy problems
don't let reproductive stock graze on too much clover

continuing after break
skipped some slides for lecture

medical dose of soy
4 glasses soy milk
1/3 brick tofu
1/2 cup edamame
1 cup soy nuts
soy powder: variabel

black cohosh
actea racemosa (not cimicifuga anymore)
phytoest and triterpene glycosides
used widely for menopause many forms
does not stim excessive endometrial prolif

GONADOTROPIC AGENTS
plants may affect pituitary and hypothalamus
stim release of FSH, LH, TSH, ACTH
dopamine inhibits prolactin: decreases excessive hormonal releases
stress-->cortisol-->insufficient dopamine and overabundant stress hormones
low dopa-->high FSH, LH, prolactin (maybe also TSH and GH)
many times pathol is dt excess hormones rather than insuff
slow transit time-->conjugated estrogen can be unconjugated and reabsorbed
general pop shows high hormonal load conditions

vitex = chaste tree berry
cimicifuga = actea = black cohosh
hypericum = St JW
melissa = lemon balm
lithosperma = stoneseed, used as herbal birth control in some cultures, prevent ovulation

CIMICIFUGA RACEMOSA = ACTEA
black cohosh
estrogenic
nervine
may affect brain endocrine

LEONURUS CARDIACA
motherwort
nervine
for hyperthyroidism, reduce elevated TSH
uterine tonic
vascular tonic
for all sx of hyperthyroid: high BP spike, irrit, nervous, fast heart, etc
protects endothelium from oxidative damage
pos affect on platelets

MELISSA CITRONELLE
lemon balm, gladdening herb
may have dopamine effect
may affect pit release of prolactin
may have calming mood effect via limbic system

VITEX AGNUS CASTUS
monk's pepper or chaste tree berry
used to decrease male libido
also for adolescent acne in males, skin complaints
may stim LH release from pit
***progesteronic effect "enhances prog"
ace in the hole all purpose female herb
breast probs, fibroids, etc all high est
foundation in many of her herbal formulas
she gets vitex fresh ground and encapsulated for her practice
dose: fairly low, a dropperful 60 drops or 1/2-1 tsp 1-2x daily

UTERINE TONICS

VIBURNUM OPULUS
cramp bark
uterine antispasmodic, tonic, anti-inflammatory
***if it doesn't work for uterine cramps, consider other etio for pain
may be engorgement, vascular congestion-->back ache for 3 days before period
may be ovarian irrit
may be bowels or sacral nerve roots
ACE IN THE HOLE for menstrual cramps
if predictable cycle, start the afternoon or night before to prevent discomfort
if irreg cycle take when sx arrive, dose every 30 mins-1 hour for acutes
mabye 3-4 doses/day to prevent
if DUB or fibroids also good
if cycle gets long in peri, this may be esp helpful
PRUNIFOLIUM is another sp, AMERICANUM
good ornamental shrub in herb garden

CAULLOPHYLLUM THALICTROIDES
blue cohosh
for uterine cramps and for atony
if hx of multi childbirths may see atony, heavy bleeding, prolapse
tensile strength of uterine muscle is part of what controls bleeding so atony-->bleeding more
for chronic miscarriage
(also vitex)
uterus hyperexcitable and implantation difficult, use this and viburnum
uterus atonic and not responding, use this and viburnum

VASCULAR TONICS

ANGELICA SINENSIS
dong quai = tong qui
researched for circ benefits
incr circ in pelvis
incr metabolism in female reprod organs
for vascular congestion
blood mover
UMBEL family

GINKGO BILOBA
maidenhair tree

CRATAEGUS MONOGYNA
hawthorne
for postmenopause and increasing HTN
other spp many

FOR MENOPAUSAL BLEEDING IRREG, premenopausal DUB, breakthrough bleeding
vitex: raise prog
achilia: tone uterus, control bleed (ACE IN HOLE TO STOP BLEEDS anywhere)
(may also vasoconstrict in uterus and core, vasodilates periphery)
viburnum: tone uterine muscle, if there's atony
cinnamomum: control heavy bleeding, vasodilate periphery, also anti DM
mix and match ingredients, dose hourly if hemorrhagic or 3x daily to shorten menses overall
shepherd's purse, capsella is also on list of styptics/hemostatics

HOT FLASHES: this is a great formula
cimicifuga: weak estrogenic action, more if also irrit
vitex: weak prog actiona
salvia: estrogenic, cooling, drying, most imp part of formula
vitamin E: support endogenous syntehsis of reprod hormones
can add nervines if needed
dose: 3-4 droppers/day for 2-3 mo then taper and see if effects are maintained
go to 2x/day or take weekends off
maintain crusing speed dose long term

dry vagina is hardest menopausal issue to tx with herbs
she uses est suppositories, E3 only
daily dose tapering down to occasional dosing (weekly, less) for dyspareunia etc

PROGESTERONE CREAM
she doesn't like it
helps temporarily
many conditions are high est, people use prog cream and feel better
later feel worse even with doubling of dose
aromatase in skin converts to est, enzyme gets upregulated-->more est
cream doesn't fix original problem
leaves pt with both high est and poss high prog
better tx: reduce est activity with herbs

PROG HERBS

DIOSCORREA
wild yam
DHEA can get shunted into stress hormones with none leftover to make sex hormones
tx stress and sex hormones increase

OSTEOPOROSIS OPTIONS
soy
red clover
black cohosh
medicago
iprilflavone: from soy but more steroidal, this is semi-synthetic, 200mg 3x/day
promotes calcium intake into bone and reduces bone breakdown
Ca, Mg, phosphorus, minerals
vitamin D3
vitamin K: supports trabecular/spongy bone, decreases clots in microvasculature
black macca

INDOLE 3 CARBINOLS and DIM
for reducing est
est metab into several hydroxyesterones
in many plants
di-indolymethan
in brassica
helps enzymatically degrade estrogen
favor metabolism into b9 est

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