Female BHRT

TRIAD 5
Copyright © 2010 Integrative Health Resources,
Inc. All rights reserved. No part of this material may be used or
reproduced in any manner whatsoever, stored in a retrieval
system, or transmitted in any form, or by any means, electronic, mechanical,
photocopying, recording or otherwise, without prior permission of the author.

This material is provided for educational and informational purposes only to

licensed health care professionals. This information is obtained from sources
believed to be reliable, but its accuracy cannot be guaranteed. Herbs and other
natural substances are very powerful and can occasionally cause dangerous
allergic reactions in a small percentage of the population. Licensed health care
professionals should rely on sound professional judgment when recommending
herbs and natural medicines to specific individuals. Individual use of herbs and
natural medicines should be supervised by an appropriate health care
professional. The use of any specific product should always be in accordance
with the manufacturer’s directions.
Female BHRT

Robert Seik, PharmD, FAARFM

Archetypes

• Women: Peri-menopausal to early post-

menopausal BHRT
• Trouble shooting
Barb Hiltz

• 52 y/o executive who feels like she is losing her “edge” at

work. She has been experiencing menopausal symptoms
of hot flashes and night sweats that now interrupt her sleep.
Mood and energy are deteriorating. Cognition is not as
sharp as it used to be which makes her nervous.
• Energy and recovery are diminished
• Weight gain has begun, historically very trim
• Concerned about bone density as she ages
The natural course of time
• By age 35, 50% of all American women are “estrogen dominant”
Glaser R, Dimitrakakis C. Testosterone therapy in
women: Myths and misconceptions. Maturitas.
2013;74:230-234.
Myth 2
• Testosterones only/main role in
women is sex drive and libido
Androgen receptors & aromatase
• Breast, heart, blood vessels
• GI tract, lung, bronchial epithelium, kidney, liver,
adrenal glands, pancreas
• Brain, spinal cord, peripheral nerves
• Bladder, prostate gland
• Uterus (endometrium, myometrium), vagina
• Ovaries (testicles), clitoris (penis)
• Endocrine glands, adipose tissue
• Skin, bones, bone marrow, synovium, muscle

T declines with age in BOTH sexes

Symptoms of Androgen Deficiency
Pre and postmenopausal women, and men
• Diminished sense of well-being
• Dysphoric mood (sadness, depression, anxiety,
irritability, restlessness)
• Persistent, unexplained fatigue
• Sexual function changes including decreased
libido, sexual receptivity and pleasure
• Vasomotor instability (hot flashes)
• Bone loss
• Decreased muscle strength
• Changes in cognition, mental focus and memory
• Insomnia, sleep disturbance
Symptoms of Androgen Deficiency
Pre and postmenopausal women, and men
• Aches, pain, stiffness
• Auto immune disease
• Menstrual/Migraine headaches
• Loss of self confidence, assertiveness
• Fat accumulation breast, abdomen and hips
• abdominal obesity
• Wrinkles, dry thinning skin and hair, brittle nails
• Incontinence, frequency, nocturia
• Vaginal atrophy, dryness
• Rapid aging and more (GI, Lungs etc.)
Who “qualifies” for BHRT?

• PAP - negative in past year

– Prior dysplasia treated with folic acid
– Cone biopsy or LEEP, not exclusions
• Mammogram - negative in past year
– Fibrocystic changes must be stable
– Thermography acceptable if documented
• Pelvic US desired prior to Tx
Requirements

1. PAP & Mammo every 2 years

2. Pelvic US yearly
Even partial hysterectomy patients - ovaries
3. Maximum of 6 months Tx - office visit
4. Re-check labs at 12 wks, 24 wks, 6
months and yearly (general schedule)
5. Sign consent form
Breast Cancer History

• Involve their oncologist or PMD in the

discussion to defuse concerns
• BHRT candidates if they are two years
cancer free. Progesterone alone, anytime.
– Except for testosterone + anastrazole pellets
• Reduce future cancer risks by addressing
lifestyle habits, diet, etc.
– Waking The Warrior Goddess - Dr. C. Horner
Guide - Don’t Push

• Educate patients to options and benefits of

BHRT but ultimately THEY choose
• Consent form essential
• Warn them of rocky road ahead
• Give plenty of articles or books to read
– Dr. Christiane Northrup “Secret Pleasures”
– Suzanne Somers
Consent Form

• This is NOT the “standard of care”

• Reasonable intelligence required to follow
this protocol (the patients IQ)
• Be cautious in who you choose to work
with, and set appropriate expectations
• “Suzanne Somers said . . . “
Why BHRT?

• Benefits - the big three

Heart - Bone - Brain
• How long? Determine patients desire
– Short term - “hot flashes”
– Long term

The benefits abate as soon as you stop

Other Benefits of Estrogen

• Insulin sensitivity • Improves mood

• Skin collagen • Enhances energy
• Increases HDL • Colon cancer ⇓⇓
• Decreases LDL • Sex drive
• Alzheimer's ⇓⇓ • Magnesium uptake
• Lowers BP • Muscle strength
• Improves sleep • Vaginal mucosa
Protocol

• Start with Progesterone for 2 to 4 weeks

before initiating estrogen
– Reverse estrogen dominance
• DIM (diindolylmethane) initiated to ensure
proper estrogen metabolism (DIM EstroNM)
– DIM is a MUST during BHRT, indefinitely
• During this time patient is to provide
PAP/Mammo/Pelvic US reports
Inst Sheet
Women: Hormone Deficiency
Progesterone DHEA
 Swollen Breasts  Fatigue, afternoon

 Anxiety  Low Libido

 Insomnia  Low Muscle Tone

 Cramping/PMS  Irritability

 Weight Gain  Urinary incontinence

 Joint Pain  Inflammation

 Irregular Cycle  Auto-Immune Diseases

Natural Progesterone
 PMS (premenstrual syndrome)
 Anxiety
 Insomnia
 Osteoporosis
 PCOS (polycystic ovarian syndrome)
 Fibroids (uterine, breast)
 Infertility (luteal phase defect)
Progestin vs. Progesterone
Side Effects
 Synthetic Progestins  Progesterone
Breast tenderness Slight to moderate
Acne drowsiness
Bloating
Depression
Vision changes
Thrombosis
Migraine
And more……….
Progesterone Dosing

• Typical production of progesterone is 20 to

30 mg per day
– Third trimester pregnancy = 400 mg/day
• Compounded cream:
– 10mg to 20mg per gram
– Dosing ½ gram to 1 gram once or twice daily
• Key: Never dose estrogen without
progesterone and consider testosterone
Estrogen options

• Estrogen initiated employing gradual build

up to avoid tachyphylaxis
• Patch provides steady release
• Creams once or twice a day (kinetics)
• Oral is unacceptable - high risk
• Pellets – not for estrogen unless,
thin/anorexic, unresolved bone loss
Vivelle Dot

• Estradiol released as 0.025 mg/day to start

and go up to 0.1 mg/day
• Increase dose every 2 weeks
• Monitor for symptoms of excess
• Decrease dose and check saliva level in 4
weeks
• Monitor progress and recheck in 12 wks
Sx of Estrogen Excess
• Breast tenderness
• Headaches
• Irritability or mood swings
• Anxiety or depression
• Puffiness or bloating
• Sleep disturbance or insomnia
• General malaise
Saliva or 24-hour Urine Test

• Topical hormones absorb into sub-Q fat and

arterioles then to tissue then vein
• Saliva/urine reflects “tissue” levels
– Measure “free” hormone, not protein bound
• Venous test does NOT reflect true level for
topically-delivered hormones
Blood VS Saliva

• Progesterone is FAT-soluble
• Bound to RBCs and Cortisol-binding globulin
in the serum (not free)
• Capillary beds filter progesterone which is
soluble in saliva
• Blood testing is inaccurate and ineffective for
monitoring progesterone levels
Goal of therapy

• Saliva estradiol between 1.3 to 3.3 pg/ml

• Progesterone 200 to 3000 pg/ml
• Ratio Pg/E2 appropriate 100 to 500
• Symptom free
• Balance clinical issues with lab
– Clinical issues most important
FSH

• Menopause = FSH of 23 or greater

• BHRT - as hormones replaced should
expect to see a fall in FSH
• FSH of below 50 is a sign of tissue response
and effective dosing
• Clinical effects still a better guide
– Monitor symptoms using assessment tools
Cycle Progesterone

• Once proper dosing levels are discovered, start

to cycle progesterone in any patient with a
uterus, regardless of age
• Pre-menopausal
– Days 7 thru 25 on progesterone
• Post menopausal
– First 5 days of month - no progesterone
Bi-Est Cream

• Estriol + Estradiol in a 80:20 or 50:50 cream

• Start with 1.25 mg (80:20) in 1 gram of
cream
• Start with 1 gram once daily for two weeks
• Increase by ½ gram per day every 2 weeks
• Monitor for symptoms
• Reduce dose and get saliva/urine test
Symptom ONLY Management

• Evamist topical spray

– Vasomotor Tx - Hot flash & night sweat
• Not adequate dosing to reach full estrogen
replacement
• 1 to 3 sprays per day - 20 to 40 pg/ml (vein)
• Vivelle Dot 0.025
Old School - Venous End points

• Serum measures of estradiol

– Goal of Tx = 70 to 100 pg/ml
• Day 21 estradiol production is 250 to 500 pg
• Looking to return to 1/3rd of youthful levels
• Saliva / urine much more accurate - E2 only
 Estrogen Metabolism
Progesterone

Sulfotransferase 17aHSD Type II

Estrone-Sulfate Estrone Estradiol
Sulfatase 17aHSD Type I

Catechol(hydroxy)
2-Hydroxy-E1 (DIM+) 4-Hydroxy-E1 (Toxins+) 16-Hydroxy-E1,2 ⇒ Estriol
Free Radicals (fats)
COMT
Methylates Quinones
Both 2 & 4
**inactivates**
4-Quinone - DNA damage - cancer
Glutathione
Binds 99% of
Quinone estrogen
**inactivates**
System Breakdown
• p450 System: anything that compromises this
efficiency will increase circulating estrogen
– Fructose and prescription drugs burden

• COMT: compromised by a lack of methyl groups or

excess estrogen production or xenoestrogens
• Glutathione deficiency
– Rancid oils, flax seed oils, oxidative stress
– Excess hormones “Premarin”
– Pesticides, solvents, pollutants
– Heavy metals
– Prescription medications
Promoting the 2-Hydroxy-E1
• Cruciferous vegetables - DIM
• Flax seed meal (fresh ground) - lignans
• Soy
• Moderate exercise
• Kudzu - isoflavone (daidzein)
• High protein diet / modified carbohydrate diet
• Omega 3 fats
• Folic acid, B6, B12 support pathway
Steroidogenic Pathways

Charts available with nutrient influences

• Genova Diagnostics
– www.GDX.net
• Meridian Valley Labs – 24-hour urine testing
– www.meridianvalleylab.com
• Metabolic Code Affiliate Library
– www.metaboliccode.com
Pelvic US

• Endometrial stripe <5mm

• If >5mm then refer patient to OB/GYN for
endometrial biopsy
• If pre-menopausal, Tx with progesterone first, if
no improvement then refer to OB/GYN
• Always get Pelvic US right after menses
• Endometrial polyp typically presents with brown-
red bleeding on a daily basis
Atypical vaginal bleed

• Low threshold for pelvic US

• Is patient cycling progesterone correctly?
• Endometrial polyp typically presents with
brown-red bleeding on a daily basis
• Punt to OB/GYN early and often when in
doubt
Breast Tenderness

Reduce 20% Yes Too low? Increase 50%

Estrogen excess Breast Tenderness Progesterone

Edema?
 No Reduce 50%

DIM & Bowel Clearance

Increase DIM Resolve constipation

Add flax meal / grnd chia seeds
Ca+D-glucarate
Breast Tenderness

• Progesterone deficiency
⇒ Corticosterone - (mineralcorticoid)
⇒ Aldosterone (inhibited by prog)

• Breast edema and tenderness

Sleep Issues

• Low and high estrogen states can interfere

with sleep
• Progesterone will facilitate sleep
– Progesterone ⇒ Pregnenolone ⇒ GABA
• Oral progesterone
– 90% liver conversion to Pregnenolone
– 50 to 100 mg PO at hs
• May be used in addition to topical
Headaches

• Excess estrogen can cause headaches

– Too stimulating
• Migraines - resolve with estrogen Tx
– Effects neurotransmitters - the amines
– Increases blood flow & oxygen delivery
– Improves neuronal function
– Reduced Alzheimers expression
Progesterone ⇒ Agitation

• Progesterone in abundance can fuel

conversion to Cortisol
• Occasionally women report agitation as a
result of stimulation of cortisol
• Check DHEA-S levels, if low then support
with 25mg po at HS to slow this reaction
– DHEA cause insomnia? Dose 25mg po in am
Progesterone ⇒ Testosterone

• Progesterone can stimulate excess

Testosterone production
• Complaints of acne or hair growth
• Tx with Testo-Quench and/or lower
Progesterone doses
– 30g of fiber per day
– Support methylation
– DIM Estro(NM): 2 bid
Progesterone Excess
• Increase cortisol and/or testosterone
• Cause insulin resistance
• Weight gain, fat storage
• Increased appetite and carb cravings
• Inhibits anti-candidal neutrophils in gut and
slows GI transport
• Down-regulates estrogen receptors in brain
leading to depression
Progesterone Capsules

• Compounded Progesterone
– 50mg, 100mg and 200mg capsules
• 100 mg dose results in 10 mg systemic
– 90% metabolized in liver to pregnenolone
• Can be used in conjunction with topical
– For sleep, use oral dose at night, 50-100mg
Soy

• Phytoestrogens -
– Isoflavones: daidzein & genistein
• Weak estrogens - 1/1000 to 1/100,000 the
activity of estradiol
• Decrease breast cancer? Mixed results
• Estrogen receptor modulator vs blocker
• Fermented vs whole vs fractionated supp
Black Cohosh

• Isoflavone formononetin - competitive inhibition

• Triterpenoid 27-deoxyactein has estrogen
effects yet stimulates apoptosis in cancer
• Cimicifugoside - affect the hypothalamus-
pituitary system and release of hormones.
• Estrogen adaptogen
Thyroid & BHRT

• Estrogen can decrease T4 ⇒ T3 conv

• Estrogen dominance increases TBG
– Estrogen replacement may therefore increase
need for thyroid replacement
• Progesterone competes with T3 for
heterodimer transport receptor
– Excess progesterone could decrease thryroid
stimulation (blocks T3)
Stress Incontinence

• Testosterone 2.5 mg + Estriol 5 mg per gram

– Intravaginal cream - 1 gm daily for 5 days
– Then twice per week thereafter
• Kegel exercises daily
– Red light “squeeze”
• Monitor testosterone levels
Vaginal Dryness

• Estriol 5 mg 2-3x per week intravaginal

• May add 2.5mg to 5mg testosterone for
atrophy and scarring
• Compounded as cream or as single-dose
vaginal applicators
Libido

• Testosterone 2% cream - topical cream

– Apply pearl sized dab to clitoris 3x/week
– If too intense then apply to labia
• Scream Cream - aids climax
– Sildenafil + Aminophylline + Arginine +
peppermint (tingle factor)
– Apply to clitoris pre coitus
– Testosterone may be added