Randomized control trials Observational Studies

Four stages of Transition:
1. Early pre-menopause
2. Later pre-menopause
3. Early post-menopause
4. Late post-menopause
May begin up to 10 years before periods
stop
 Characterized by too much estrogen, not
enough progesterone and normal
testosterone
 Symptoms: PMS, breast symptoms, brain
irritability, sleep disturbance and occasional
hot flashes, heavy periods, endometriosis,
fibroids [this is when breast cancers start]
 Sometimes referred to as “estrogen
dominance”

Prevent cortisol steal by stress reduction
Chaste berry herbal supplementationdecreases prolactin and may increase
progesterone
 Bioidentical progesterone (progestins will
not work; OCP’s may help by lowering
estrogen or hurt by lowering
progesterone)
 Decrease relative estrogen levels by
decreasing inflammation and by
improving estrogen metabolism and
excretion
 Even out fluctuations with isoflavones


Novel
 Unexpected
 Threat to the ego
 Sense of loss of control

QuickTime™ and a
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Usually within 1-2 years of cessation of
periods
 Characterized by wildly fluctuating or
falling levels of hormones
 Symptoms vary depending upon
hormone levels at the moment, irregular
periods less flooding, more hot flashes, a
variety of symptoms mostly brain

From the cessation of periods to about 48 years post-menopause (age 60)
 Falling levels of estrogen, low
progesterone (made mostly by the
adrenals), variable levels of testosterone
 Symptoms: more hot flashes, weight
gain, sleep disturbance, less hormonal
flexibility and therefore ability to deal
with stress

Menopause
From around age 60-65 onward
 Characterized by low estrogen, falling
levels of testosterone and variable levels
of progesterone
 Symptoms: Vaginal dryness, thin skin with
more wrinkles, increased cardiovascular
disease and brain dysfunction, more
breast “sagging”

Tina Turner at 68
Actress Helen Mirren at 64
Healthy Longevity!

1. Menopause is an illness and needs to
be treated.
1. Menopause is an illness and needs to
be treated.
 2. The untreated menopause causes
aging (Wilson-Feminine Forever)

1. Menopause is an illness and needs to
be treated.
 2. The untreated menopause causes
aging (Wilson-Feminine Forever)
 3. Women exist to reproduce. At
menopause their bodies become tools
of self-execution. (Wylie)

1. Menopause is an illness and needs to
be treated.
 2. The untreated menopause causes
aging (Wilson-Feminine Forever)
 3. Women exist to reproduce. At
menopause their bodies become tools
of execution. (Wylie)
 Menopause is a time of empowerment

A teaching moment - adrenal bank
account
 A life stage - who am I?
 Ignore the message…at your peril!depression, anxiety, insomnia

1. Menopause is an illness and needs to
be treated.
 2. The untreated menopause causes
aging (Wilson-Feminine Forever)
 3. Women exist to reproduce. At
menopause their bodies become tools
of execution. (Wylie)
 Menopause is a time of empowerment
 Fix what’s broke; if it ain’t broke, don’t fix
it!

Fig 1. Yearly rates of prevalence of estrogen-only and estrogen/progestin-containing hormone therapy
use and incidence of invasive first primary breast cancer in Kaiser Permanente-Northern California
(KPNC) members, the 13-county KPNC catchment area, and the state of California, from 1994 to 2004
Clarke, C. A. et al. J Clin Oncol; 24:e49-50e 2006
Copyright © American Society of Clinical Oncology
Age at enrollment
Randomized control
trials
Observational Studies
>62
30-55
Time since menopause >10
<6
Duration of therapy
<7
>10
Menopause sx (hot
flashes)
excluded
Predominant
BMI
~29
~25
From Medscape Ob/Gyn & Women's HealthThe Beneficial
Effect of Hormone Therapy on Mortality and Coronary Heart
Disease in Younger versus Older Postmenopausal
WomenHoward N. Hodis, MD; Wendy J. Mack, PhD Posted:
02/29/2008






Women who have abnormal hormone
levels for their age:
Most women who have had ovaries
removed
Some women who have had uterus
removed
Women with very low cholesterol
Women with hormone imbalance that
can’t be fixed in other ways
Women with SEVERE symptoms that can’t
be addressed in other ways
 S/P
oophorectomy
 Autoimmune destruction of the
ovary
 Low estrogen output due to
balancing other hormones
H = Hypothalamus (neural/immune tissue)
 P = Pituitary (neural/immune and
endocrine tissue)
 A = Adrenal (endocrine tissue)
 T = Thyroid (endocrine tissue)
 G = Gonadal (endocrine tissue)
 G = Gut (immune tissue of the gutassociated lymphoid tissue)

Brain and
emotional effects.
Prefer sweets
Calorie storage
Intuition and
mothering
behavior
Resistant
cardiovascular
system
Calorie
conservation
Estrogen
Monthly cycles
Ovulation, endometrial
preparation
Skeletal support
Preparation for
breastfeeding
Estradiol E2
Estrone E1
Estriol E3
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…women identify many reasons they are
sexual over and beyond inherent sexual
drive or “hunger.” Women tell of wanting to
increase emotional closeness,
commitment, sharing tenderness, and
tolerance, and to show the partner that he
or she has been missed (emotionally or
physically).
Basson R, Obstet gynecol 2001;98:350-3.
Patients report greater satisfaction
 Progesterone is associated with decreased
breast cancer risk than progestins
 Estriol may decrease risk of breast cancerstudies are needed
 Progesterone decreases cardiovascular risk
compared to progestins


Holtorf K. Postgrad Med. 2009 Jan;121(1):73-85.
The Problem with Salivary Hormone Levels

Eat better
Vegetables!
Brassica, Gogi, Soy (non-GMO), Curcumin,
Resveratrol, Quercitin
 Protein/Carb balance—watch the sugar
 Avoid obesity, diabetes
 Don’t skip meals
 Healthy fat—a note about cholesterol
levels

Eat better
 Get your “beauty sleep”

Asleep within 30 minutes of lights out
 Sleep through the night
 Awaken without an alarm clock
 Sleep around 8 hours
 Don’t need a nap the rest of the day

Eat better
 Get your “beauty sleep”
 Exercise appropriately

Eat better
 Get your “beauty sleep”
 Exercise appropriately
 Reduce stress

Novel
 Unexpected
 Threat to the ego
 Sense of loss of control

Eat better
 Get your “beauty sleep”
 Exercise appropriately
 Reduce stress
 Measure your hormone levels

Fig. 1. Schematic of the hypothetical rationale for the design of the Kronos Early Estrogen
Prevention Study (KEEPS) based on studies of nonhuman primates
Miller, V. M. et al. J Appl Physiol 99: 381-383 2005;
doi:10.1152/japplphysiol.00248.2005
Copyright ©2005 American Physiological Society
Researchers in Colorado have made a startling discovery.
Fish, apparently male, are developing female sexual
organs. Scientists believe it's the result of too much
estrogen in the water and they're finding estrogen in
rivers across the country.
"I've done a lot of studies throughout my career which
extends back to 1973," says research associate John
Woodling. “This is the very first time that what I've found
scared me."
"This fish has characteristics of both male and female," says
Dr. David O. Norris of the University of Colorado,
Boulder.
Researchers say the cause is too much estrogen in the
water, which is found in every sewer system. But also, they
say, certain chemical compounds in detergents and
soaps can mimic estrogen.
 Barbara Biggs, of Denver's largest sewage plant, says
most of the nation's sewage plants simply can't remove
all the estrogen in the water.
 "We're concerned about the effect on aquatic life, but
we're also concerned about our ability to actually treat
for these estrogens and estrogen mimickers," says Biggs.
 They’ve been banned in much of Europe and are under
review in Canada, but are still common in America,
where they are flowing out of sewage plants and into
clean water flowing into America's rivers.
 Government researchers recently found natural
estrogens and estrogen mimickers in 80 percent of the
streams they tested in 30 states.

Endogenous Hormones and Breast Cancer Collaborative Group. J NCI 2002;9
Laughlin GA. J clin endocrinol Metab 2000;86(2):645-51
 Follicular
phase [20-40pg/mL]
 Luteal phase [60-80pg/mL day
21]
 Perimenopause [all over the
map]
 Menopause early[15-25pg/mL]
 Menopause late [5-15pg/mL]
What you get is determined by:
1. Genetics
2. What enzymes are up or down
regulated
3. What you put in
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Androstenediol
Estrogen
Receptor
Estrone
Estradiol
17 HSD
DHEA
Androstenediol
17 HSD2
3 HSD
isomerase
3 HSD
isomerase
17 HSD5
Androstenedione
Testosterone
17 HSD6,2
Arom
Arom
17 HSD1
Estrone
Estradiol
17 HSD2
STS
STS
SULT
STS
E1S
SULT
STS
E2S
17 HSD1
DHEA-S
Adiol-S
17 HSD2
Estrogen Production/Metabolism
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2
17 HSD1
17 HSD1
Bradlow HL. J Endocrinol 1996;150:s259-s263.
Estriol and competitive inhibition of estradiol
receptors as rationale for use
 Both agonist/antagonist effects on estradiol
receptors
Melamed M, et al. Mol Endocrinol 1997
Nov;11(12):1868-78
 Usual ratio in compounded formulas is
80%estriol/ 20%estradiol, given oral or
topical

It is an estrogen
 It needs to be studied more
 Taken orally with estradiol, it is an antagonist-why
give both?
 Unknown dynamics in breast tissue
 Taken vaginally it is very useful in the treatment of
atrophic vaginitis and may be safer than estradiol as
it has little effect on the endometrium
