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6/24/2016
Diagnosis and Management
of Women’s Top Complaints:
Insomnia, Fatigue, Weight
Gain and IBS
Treating Hormonal imbalances and menopause
with root-cause corrections
ERIN LOMMEN ND
CEO AND ASSOC. MEDICAL DIRECTOR
LABRIX CLINICAL SERVICES
Charlotte 49 yo female
(Referred to me by her Chiropractor)
01/2011
Chief Complaints
Fatigue 1-10(worst) 1-2
Insomnia 1-10(worst) 3 (cannot fall nor stay asleep)
GI complaints 1-10(worst) 2 (7-10 loose bm/day)
Weight Gain (Belly fat) 35 lbs in two years
Frequent menses with heavy bleeding (q 14-20 days)
05/2012
Recently put on disability from work
Charlotte
HPA Axis Phase III adrenal support protocol with light therapy
Topical Progesterone 40-50mg daily for 3 weeks/one week off
Dim light two hours before bed, melatonin/l-theanine combo
Gut testing-treated for “IBS”
LGI Nutrition
Rest every two hours (x 15 mins)
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Charlotte, 52yo F | Cortisol series
2008
4/2011
9/2011
5/2012
12/2012
Educational Objectives
•Review of Women’s Health Complaints, clarifying misconceptions and
demographics for Women’s Health
•Receive a brief overview for Hot Flashes
•Gain a comprehensive understanding of Insomnia, Fatigue, Belly Fat(Insulin
Resistance) and IBS and their multifaceted impact on overall health
•Learn up-to-date diagnostic assessments and interpretation of these results for
state-of-the-art Treatment solutions
•Lifestyle Interventions for Hormonal Balance and Successful strategies for
correcting common conditions by testing and treating with bioidentical
hormones
•Clinical Pearls
Symptoms of HPA Axis Dysregulation;
Adrenal Fatigue (adrenal dysfunction)
• Low body temperature • Insomnia
• Low blood pressure
• Unexplained hair loss
• Indigestion/IBS
• Craving sweets
• Poor memory
• Headaches
• Weakness
• Moments of confusion • PMS
• Nervousness
• Feelings of frustration
• Excessive hunger
• Irritability
• Mental depression
• Lack of energy
• Alternating diarrhea
and constipation
• Poor resistance to
infections
• Difficulty building
muscle
• Hypoglycemia
• Osteoporosis
• Dry and thin skin
• Decreased Libido
• Low blood pressure
• Apprehension/Anxiety • Light headedness
• Dizziness that occurs
upon standing
• Palpitation (heart
fluttering)
• Food / Inhalant
allergies
• Tendency towards
inflammation
• Inability to
concentrate
• Issues with weight
Wilson JL. Adrenal Fatigue: The 21st Century Stress Syndrome. Petaluma, CA: Smart Publications; 2001.
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Symptoms of Progesterone Deficiency
Mood swings
Bone Mineral Loss (Osteoporosis)
Depression
Lack of Concentration
Irritability
Short-term Memory Loss
Irregular Periods, Heavy Menstrual Bleeding
Dry, Thin, Wrinkly Skin
Hot Flashes/Night sweats
Thinning of Scalp Hair
Vaginal Dryness
Increased Facial Hair
Water Retention
Diffuse Aches and Pain
Decreased Libido
Weight Gain: Hips, Thighs and Abdomen
Headaches
Breast Tenderness/Fibrocystic Breasts
Fatigue
Uterine Fibroids
Sleep Disturbance (Insomnia, less REM sleep)
Infertility
Symptoms of Neuroendocrine
Imbalances:
Mood problems such as
Depression and anxiety
Low physical energy and
stamina
Appetite control, insulin
resistance
Fatigue and sleep
disorders
Addiction and
dependency
Low pain tolerance
Poor mental focus, or
ADD, ADHD
Low libido
Sexual dysfunction
1.
2.
Depression and anxiety symptoms are related to increased 24-hour urinary norepinephrine excretion among healthy
middle-aged women. Hughes JW, et al. J Psychosom Res. 2004; 57: 353-58.
Blood serotonin levels in postmenopausal women: effects of age and serum estradiol levels. Gonzales GF, Carillo C.
Maturitas. 1993;17:23-9.
See anything in common?
FATIGUE
ANXIETY
IRREGULAR
PEROIDS
CARBS
CRAVINGS
WEIGHT
GAIN
DECREASED
LIBIDO
IRRITABILITY
POOR SLEEP
DEPRESSION
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Stress Response
When a stress response is triggered, the HPA axis is stimulated to produce cortisol and DHEA in the adrenal
cortex, and the adrenomedullary hormone system initiates norepinephrine and epinephrine production in
the adrenal medulla. Initially, these neurotransmitter levels tend to be elevated – often causing a
concomitant rise in inhibitory neurotransmitters such as GABA. Additionally, cortisol is required in the
conversion of norepinephrine to epinephrine, so a compromise in cortisol levels (as seen with chronic
stress) causes an imbalance in the ratio between these two neurotransmitters.
The US population
is not getting any
younger…
Women’s life expectancy has increased
from age 47 in 1900 to age 81 by 2015.
This translates into nearly thirty five
years of life after menopause! Millions
of women in the USA have decided it is
time to get serious about hormone
balancing and health optimization for
the long-term.
Toro R. Global life expectancy (infographic), life expectancy around the world. Available from http://www.livescience.com/22005-highest-and-lowest-life-expectancy-at-birthinfographic.html. Accessed October 30, 2014.
Mead JH, Lommen ET. Slim, Sane & Sexy: Pocket Guide to Natural, Bioidentical Hormone Balancing. Rancho Mirage, CA: Fountain of Youth Press: 2009.
Hormone transitions :
menopausal symptoms and
accompanying conditions
•Impacts 25 million women worldwide annually, and an estimated 1.2 billion women
are projected to be postmenopausal by 2030
•In the US 11,000 Americans are turning 50 every day
•By 2020, 40% of the US population will be 60 years old
•As the Baby Boomer population passes ages, an unprecedented 6000+ women are
estimated to reach menopause every day!
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Major hormones that affect women
during hormonal transitions
Estrogens
Progesterone
Testosterone
DHEA
Cortisol
Melatonin
Women with hormone imbalances experience hot
flashes and night sweats and numerous other
complaints... insomnia, fatigue, weight gain
(especially belly fat) and IBS.
Where to begin?
Treat root causes: neuroendocrine imbalances
Hormonal
Adrenal
Neurotransmitters
Gut health
In past decades, one size fit all
Menopause Symptoms =
HRTrx (and same dosage)
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Usual Care model
Is the patient
postmenopausal?
Yes
Give her
Premarin and
Provera
No
Has she had a
hysterectomy?
No
Give her a birth
control pill
Yes
Give her
Premarin
Symptoms
resolved?
No
Add an
antidepressant
Fast forward to present: 2016
Functional Testing targets and defines individualized
treatment approach
Compounding Pharmacy crafts bioidentical hormone
supplements- tailored to each individual
Bioidentical Hormones (numerous options) are available
OTC and from pharmaceutical manufacturers
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When do our Hormones
Decline?
Perimenopause (age 40 on up): Estrogen
decreases to ⁄ to ⁄ of that of baseline
levels (reproductive years) whereas
progesterone decreases to about ⁄ of
previous reproductive levels.
Lee J. What Your Doctor Didn’t Tell You About Menopause: Balance Your Hormones and Your Life from Thirty to Fifty. New York, NY: Warner Books; 2004.
Hormonal Decline with
Menopause
Progesterone declines at a MUCH faster rate than estrogen during
peri-menopause
Lee J. What Your Doctor Didn’t Tell You About Menopause: Balance Your Hormones and Your Life from Thirty to Fifty. New York,
NY: Warner Books; 2004.
Inaccurate generalization made by
many Practitioners
(because they both bind the progesterone receptors)
Progestins are not Progesterone
– They have a different molecular structure
– Progestins do not have the same effects as
bio-identical progesterone
– Progestins have many negative side effects
– Progesterone has positive anti-aging,
disease-preventative effects
Fournier A, et al. Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. Int J Cancer. 2005; 114: 448-54.
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Progesterone v Progestin
Progesterone
Medroxyprogesterone Acetate
Are hot flashes a symptom of
estrogen deficiency
OR
estrogen dominance?
Both!
Hot flashes and night sweats are associated
with: Fluctuating estrogen
Low estrogen levels
High estrogen levels
And/or low progesterone levels.
Leonetti HB, Longo S, Anasti JN. Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss. Obstetrics and Gynecology 1999;94:225-8.
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Hot Flashes & Menopause
75% of women experience hot flashes at some point during
the menopausal transition
Severity ranges from annoying to debilitating
Increase in frequency during perimenopause, peak during
first 2 years postmenopausal with gradual decline over
time…usually*
Duration from 6 months to 14 years
The North American Menopause Society. http://www.menopause.org/for-women/sexual-health-menopause-online/causes-of-sexual-problems/hot-flashes. Accessibility verified 2/16/15.
A study of 1449 women with frequent
(> 6 days in the previous 2 weeks)
vasomotor symptoms (VMS)
•Mean VMS duration of 7.4 years
•Pre/perimenopausal at onset of VMS had longest VMS duration
(median 11.8 years)AND greatest persistence postmenopausally
(median 9.4 years)
•Postmenopausal onset shortest duration (median 3.4 years)
•African American women reported longest VMS duration (median 10.1
years)
Avis, PhD, et al. Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition. Jama Intern Med. Feb 16, 2015 (Epub ahead of print).
Conclusions
•Frequent VMS lasted more than 7 years during menopausal
transition for more than 50% of women and persisted for
4.5 years after the final menstrual period
•“Health care professionals should counsel women to expect
that frequent VMS could last more than 7 years, and they
may last longer for African American women.”
•…or advise them to seek healthy sustainable solutions!!
Avis, PhD, et al. Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition. Jama Intern Med. Feb 16, 2015 (Epub ahead of print).
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Estradiol concentrations and working memory
performance in women of reproductive age.
OBJECTIVE: Estrogen has been proposed to exert a regulatory influence on the
working memory system via actions in the female prefrontal cortex.
METHOD: Women were retrospectively classified into low- or high-estradiol groups
based on the results of radioimmunoassays of saliva collected immediately before
and after the cognitive testing.
RESULTS: Pearson's correlations showed that the level of salivary estradiol but not
progesterone was correlated inversely with the number of working memory errors
produced. Women tested at high levels of circulating estradiol tended to be more
accurate than men.
CONCLUSIONS: Consistent with previous studies of postmenopausal women, higher
levels of circulating estradiol were associated with better working memory
performance.
Hampson E, Morley EE. Estradiol concentrations and working memory performance in women of reproductive age.
Psychoneuroendocrinology. 2013 Dec;38(12):2897-904. doi: 10.1016/j.psyneuen.2013.07.020. Epub 2013 Aug 22.
Treatment Options
Supplements
•Vitamin E: 400-800 iu daily – may reduce occurrence and
severity of hot flashes and night sweats while offering
immune and cardiovascular support
•B vitamins, Vitamin C, magnesium and potassium
•Evening Primrose Oil: 500 mg tid – shown to reduce night
time flushing
•Black Cohosh: 40-80 mg qd – at least 4-12 weeks of
treatment may be required before therapeutic benefits are
seen
“Physical exercise and vasomotor symptoms in post- menopausal women.” Ivarsson T, Spetz AC, Hammar
Androgens and estrogens in relation to hot flushes during the menopausal transition.” Overlie, I., et al Maturitas. 2002 Jan 30; 41(1):69-77.
Chenoy R, Hussain S, Tayob Y, et al. Effect of oral gamolenic acid from evening primrose oil on menopausal flushing. BMJ 1994;308:501-503.
“Antiestrogenic activities of Cimicifuga racemosa extracts” Zierau O, Bodinet C, Kolba S, et al. J Steroid Biochem Mol Biol 2002;80:125-130.
Add Intake questions
Insomnia
Fatigue/HPA Axis Dysfunction
Weight Gain
IBS
Do you awaken rested?
Do you have trouble falling asleep or staying asleep (How many nights per
week?)
On a scale of 1-10 (10 being best), what is your overall energy level …day to day
on average?
◦ What was it 1 year ago —When did you feel the best you have ever felt?
Is there a time of day that is better? Worse?
Is your weight gain mainly in one area (breast /hips/Belly region)
Is your body type similar or dissimilar to female family members (Mom, older
sister, Aunts). What has their hormonal history been (age of menopause,
PCOS? Insulin Resistance issues, E2 dom )?
How many bm’s do you have per day-formed/loose? (not any GI complaints*)
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Laboratory Testing for Top Complaints
Fatigue
Weight Gain
Adrenal Function Panel-Salivary
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Sex Steroid Hormones
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Neurotransmitters-Urine
Testing Recommended for:
(Four timed cortisol & DHEA, saliva)
(Estrone, Estradiol, Estriol, EQ, Progesterone,
Pg/E2, Testosterone and Melatonin )
(Dopamine, Serotonin, Norepinephrine,
Epinephrine, urine)
DNA Testing
(saliva)
Serum Testing
(CMP, CBC, Thyroid, Vit D, Lipids, B12, folate)
Mood/Depre Insomn
ssion/Anxiet
ia
y
IBS
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Best method for
gathering information
during Women in
Hormonal Transition
Pin donated with the Birth Home, Inc. Records to HC&A41
41 Birth Home, Inc. Records, Accession no. 2014-01
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INSOMNIA
INSOMNIA-impacts health, work
performance and overall well-being
and quality of life
•Persistent disorder that can make it difficult to fall asleep,
stay asleep, awakening too early in the morning and unable
to return to sleep or aspects of many or all despite the
opportunity for adequate sleep
•Awakens feeling unrested, unrefreshed
•May take a toll on ability to function throughout the day
•Diminishes waking day energy levels
•May cause depressed mood
•May have serious Clinical Consequences
INSOMNIA
National Sleep Foundation Poll and National Sleep
Foundation
•Being female is a STRONG risk factor
•57% of women experienced one or more
symptoms of insomnia -a minimum of a few
nights a week
•61 % of menopausal women have sleep
problems
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Over 61% of postmenopausal
women report insomnia
symptoms!
National Sleep Foundation. http://Sleepfoundation.org/sleep-topics/menopause-and-sleep. Accessibility verified 12/8/2014
Insomnia-Underdiagnosed
and Undertreated
•Only 1/3 of women experiencing insomnia will
report it
•Women aged 45-64 are most likely to experience it
and to seek help for it (Joffe et al and Young et al,
2003)
Insomnia differential diagnosis
Chronic
◦
◦
◦
◦
◦
◦
◦
Disordered breathing
Circadian rhythm disorder
Restless leg syndrome
Nocturnal myoclonus
Neurological disease
Chronic Illnesses
Drug intoxication
Transient
◦ Life stressors
◦ Jet lag
◦ Stimulants
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Most Cases of Insomnia in
Peri-Menopause and Menopause
are related to:
•Hormone Imbalances
•HPA axis dysfunction
•Neurotransmitter Imbalance
•Melatonin insufficiency and irregularity
Sleep predicts survival of Women
with Advanced Breast Cancer
The women with the highest sleep efficiency scores survived an average of 68.9
months, while the inefficient sleepers survived just 33.2 months.
These findings show that better sleep efficiency and less sleep disruption are
significant independent prognostic factors in women with advanced breast cancer.
Further research is needed to determine whether treating sleep disruption with
cognitive behavioral and/or pharmacologic therapy could improve survival in women
with advanced breast cancer.
We were surprised by the magnitude of the relationship between sleep quality and
overall survival even after we accounted for medical and psychological variables that
typically predict survival,” lead author Oxana Palesh, Ph.D., assistant psychiatry and
behavioral sciences professor at Stanford University and research director of the
Stanford Cancer Survivorship said in a statement
disrupted sleep may impair immune system function.
Consistent short sleepers are at a higher risk of dying of any cause than people who
get sufficient sleep each night, according to a 2010 study. And a 2012 study found
that regularly getting too little sleep may also increase a woman’s risk of developing
aggressive breast cancer.
Lack of sleep is linked to more
aggressive breast cancers in
Menopausal Women
•the study is the first-of-its-kind to show an association between
insufficient sleep and biologically more aggressive tumors as well as
likelihood of cancer recurrence
•asked about the average sleep duration in the last two years.
Researchers found that women who reported six hours or less of sleep
per night on average before breast cancer diagnosis had higher
Oncotype DX tumor recurrence scores. The Oncotype DX test assigns a
tumor a recurrence score based on the expression level of a
combination of 21 genes.
•Short sleep duration is a public health hazard leading not only to
obesity, diabetes and heart disease, but also cancer
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Melatonin
“Sleep Hormone”
Melatonin: Characteris0cs, Concerns and Prospects Josephine Arendt. Journal of Biological
Rhythms, Vol. 20 No. 4, August 2005. 291-303. Literature review
Long-term monitoring of human rhythms
◦ Primary and essential function of melatonin in mammals is to
convey information concerning day length to body physiology
for the organization of day-length-dependent seasonal
functions.
◦ It is the only humoral method of signaling time of day and year
to other physiologic systems.
◦ Timing, amplitude and details of melatonin profile is highly
reproducible from day to day, even without strictly controlled
sampling conditions.
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In addition to receptor mediated actions, congruent with other tissues,
melatonin influences the physiology of all ovarian cellular components via
stimulation of antioxidative enzymes and its multifaceted free radical
scavenging activities
Melatonin levels were two times higher in large human follicles just prior
to ovulation compared to those in smaller antral, immature follicles. The
authors speculate that because melatonin and its metabolites are such
potent antioxidants, the elevated melatonin concentrations in the follicular
fluid at the time of ovulation would be physiologically advantageous. This
is because the ovulatory process has been linked to inflammation, which is
associated with high free radical production.
To protect the ovum from oxidative damage during its expulsion from the
ovary, the presence of melatonin would ensure that it escapes molecular
mutilation thereby ensuring a healthy embryo and fetus.
The origin of melatonin in the follicular fluid is the blood and from its local
synthesis in granulosa cells.
Age
• Melatonin concentrations wane as subjects age.
• The decline in pineal melatonin synthesis is accompanied by a corresponding
diminished melatonin production in peripheral organs as well.
• Since melatonin passes the placenta and has proven antioxidant actions in the
fetus, it is possible that treatment of females with melatonin during pregnancy,
especially when the pregnancy occurs late in the normal reproductive period,
may reduce certain fetal problems associated with late life pregnancies.
Melatonin, even when given at extremely high doses to pregnant rats, has not
been shown to have measurable untoward effects in either the mother or the
fetus.
• Finally, since the loss of melatonin may be part and parcel or reproductive decay
during aging, an obvious corollary is that the daily administration of melatonin,
e.g. to women approaching or entering menopause, may aid in prolonging
reproductive health in terms of becoming pregnant and delivering healthy
offspring.
Recurrent short sleep, chronic insomnia symptoms and salivary
cortisol: A 10-year follow-up in the Whitehall II study.
Although an association between both sleep duration and disturbance with salivary cortisol
has been suggested, little is known about the long term effects of poor quality sleep on
diurnal cortisol rhythm. The aim of this study was to examine the association of poor quality
sleep, categorized as recurrent short sleep duration and chronic insomnia symptoms, with
the diurnal release of cortisol.
We examined this in 3314 participants from an occupational cohort, originally recruited in
1985-1989. Salivary cortisol was measured in 2007-2009 and six saliva samples were
collected: (1) waking, (2) waking+0.5h, (3) +2.5h, (4) +8h, (5) +12h and (6) bedtime, for
assessment of the cortisol awakening response and the diurnal slope in cortisol secretion.
Participants with the first saliva sample collected within 15min of waking and not on steroid
medication were examined. Short sleep duration (≤5h) and insomnia symptoms (Jenkins
scale, highest quartile) were measured in 1997-1999, 2003-2004 and 2007-2009.
Recurrent short sleep was associated with a flatter diurnal cortisol pattern. A steeper
morning rise in cortisol was observed among those reporting chronic insomnia symptoms at
three time points and among those reporting short sleep twice, compared to those who
never reported sleep problems. Participants reporting short sleep on three occasions had
higher levels of cortisol later in the day, compared to those never reporting short sleep,
indicated by a positive interaction with hours since waking (β=0.02 (95% CI: 0.01, 0.03)).
We conclude that recurrent sleep problems are associated with adverse salivary cortisol
patterns throughout the day.
Abell JG, Shipley MJ, Ferrie JE, Kivimäki M, Kumari M. Recurrent short sleep, chronic insomnia symptoms and salivary cortisol: A 10-year follow-up in the Whitehall II study.
Psychoneuroendocrinology. 2016 Feb 26;68:91-99. doi: 10.1016/j.psyneuen.2016.02.021. [Epub ahead of print]
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Acute stress alters autonomic modulation
during sleep in women approaching
menopause.
Abstract: Hot flashes, hormones, and psychosocial factors contribute to insomnia risk in the context of
the menopausal transition. Stress is a well-recognized factor implicated in the pathophysiology of insomnia; however the impact of stress on
sleep and sleep-related processes in perimenopausal women remains largely unknown.
We investigated the effect of an acute experimental stress (impending Trier Social Stress Task in the
morning) on pre-sleep measures of cortisol and autonomic arousal in perimenopausal women with and
without insomnia that developed in the context of the menopausal transition. In addition, we assessed the macroand micro-structure of sleep and autonomic functioning during sleep. Following adaptation to the laboratory, twenty two women with (age: 50.4±3.2 years)
and eighteen women without (age: 48.5±2.3 years) insomnia had two randomized in-lab overnight recordings: baseline and stress nights.
Anticipation of the task resulted in higher pre-sleep salivary cortisol levels and perceived tension, faster
heart rate and lower vagal activity, based on heart rate variability measures, in both groups of women.
The effect of the stress manipulation on the autonomic nervous system extended into the first 4h of the night in both groups.
However, vagal tone recovered 4-6h into the stress night in controls but not in the insomnia group. Sleep
macrostructure was largely unaltered by the stress, apart from a delayed latency to REM sleep in both groups. Quantitative analysis of non-rapid eye
movement sleep microstructure revealed greater electroencephalographic (EEG) power in the beta1 range (15-≤23Hz), reflecting greater EEG arousal during
sleep, on the stress night compared to baseline, in the insomnia group. Hot flash frequency remained similar on both nights for both groups. These results
show that pre-sleep stress impacts autonomic nervous system functioning before and during sleep in perimenopausal women with and without insomnia.
Findings also indicate that women with insomnia had increased EEG arousal and lacked recovery in
vagal activity across the stress night
.
in this group
suggesting a greater sensitivity to stress
de Zambotti M, Sugarbaker D, Trinder J, Colrain IM, Baker FC. Acute stress alters autonomic modulation during sleep in women approaching menopause.
Psychoneuroendocrinology. 2016 Apr;66:1-10. doi: 10.1016/j.psyneuen.2015.12.017. Epub 2015 Dec 21.
“Sleep deprivation as a neurobiologic and
physiologic stressor: allostasis and allostatic load”
Allostatis is the process of achieving homeostasis.
Allostatic load refers to the cumulative wear and tear on body systems caused by
too much stress and/or inefficient management of the systems that promote
adaptation through allostatis
Review of literature. Chronic sleep deprivation in young healthy volunteers has
been reported to:
◦
◦
◦
◦
◦
◦
increase appetite and energy expenditure
increase levels of proinflammatory cytokines,
decrease parasympathetic and increase sympathetic tone,
increase blood pressure,
increase evening cortisol levels
elevate insulin and blood glucose.
10.1016/j.metabol.2006.07.008
“Sleep Loss Results in an Elevation of
Cortisol Levels the Next Evening”
After normal sleep plasma cortisol levels over the 1800-2300 hour period were
similar on days 1 and 2
After partial sleep deprivation evening cortisol levels were 37% higher on day 2
than day 1
After total sleep deprivation, plasma cortisol levels over the 1800-2300 hour
period were 45% higher on day 2 than on day 1.
Onset of the quiescent period of cortisol was delayed by one hour in both cases
Sleep, 20(10):865-870
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“Effects from 884 MHz mobile phone
radiofrequency on brain electrophysiology,
sleep, cognition, and well-being”
35 men and 36 women between 18-45
Double blind/placebo controlled. Some exposed to radiation that mimicked
that of cell phones, others received “sham” exposure
3 hours of exposure
Those who received radiation took longer to enter the deep stages of sleep
(stage 3)
Shortened sleep (stages 3 and 4)
“Results suggest that RF exposure, of this magnitude and duration, results in
effects indicative of non-specific activation of brain’s general arousal and/or
stress response systems.”
Laboratory Testing: Saliva
Salivary hormones
◦ Timing of collection:
◦ Pre-menopausal: mid-luteal surge (days 19-23 of a 28 day cycle)
◦ Peri-menopausal: try to catch mid-luteal surge
◦ Post-menopausal: any day
My saliva road-map which helps
define treatment
E2 deficiency
High Testosterone
Pg/E2 Ratio
High DHEA
Low EQ
High E2/Estrogen Dominance
Insufficient Progesterone
Low Testosterone
Low DHEA
HPA Axis (Phasing of Adrenal Function)
Melatonin levels and phase shifts
DHT imbalance
Suggestive of suboptimal thyroid and
insulin resistance
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Saliva Testing for Women Wanting BHRT
with Insomnia-Establish baseline levels:
Comprehensive Panel (8 hormone panel)
– E2, Pg, T, DHEA, four timed cortisols (adrenal function panel)
-plus melatonin (3-5 timed samples)
OR
Comprehensive Plus Panel and Melatonin (10 hormone panel
plus three)
(– addition of E1 and E3 and EQ to the 8 hormone panel(when High
risk family history or woman over 55)
Consideration: DHT (hirsutism, hair loss, acne)
Melatonin
sample report
Laboratory Testing: Serum
Thyroid panel
◦ TSH, fT3, fT4, with antibody
considerations (TPO, Tg Ab)
CMP and CBC
Ferritin
25-OH-VIT D
Lipids (VAP)
B12, folate
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Sleep Aids
More women than men use sleep aids
The age group with the highest prevalence of sleep
aids is 50-59 second only to ages 80+
Quality of sleep?
•Prescription sleep aids are typically hypnotics and
tend to inhibit deep natural sleep
•Prescription sleep aids may be effective at initiating
sleep but may not effect sustained sleep
An alternative…
Progesterone supplementation: PO
When progesterone is delivered orally, the vast majority is
metabolized to allopregnenolone at first pass.
Allopregnenalone works at GABA receptors, promoting an
easier time falling asleep and supporting staying asleep
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Peri/postmenopausal F
cc: sleep disturbance
Progesterone prevents sleep
disturbances and modulates GH,
TSH, and melatonin secretion in
postmenopausal women.
CONCLUSIONS:
Progesterone had no effect on undisturbed sleep but restored normal sleep
when sleep was disturbed (while currently available hypnotics tend to inhibit
deep sleep), acting as a "physiologic" regulator rather than as a hypnotic drug.
Use of progesterone might provide novel therapeutic strategies for the
treatment of sleep disturbances, in particular in aging where sleep is
fragmented and of lower quality.
Caufriez A, et al. Clin Endocrinol Metab. 2011 Apr;96(4):E614-23.
Sleep Hygiene
• Avoid going to bed unless you are sleepy.
If you’re not sleepy at bedtime, then do
something else to relax your body and
distract your mind.
• Begin rituals that help you relax each
night before bed. This can include
activities such as a warm bath, a light
snack, or a few minutes of reading.
• Get a full night’s sleep on a regular basis.
• Keep to a regular schedule.
• Avoid going to bed hungry, but also avoid
eating a big meal near bedtime. A few
grams of protein before bed can be
helpful.
• Avoid any alcohol within 6 hours of your
bedtime.
• Avoid sleeping pills. If you are using
sleeping aids regularly, even over the
counter, consult your physician.
• Avoid any strenuous exercise within 6
hours of your bedtime.
• If you are not asleep after 20 minutes then
get out of bed and find something else to
help you feel relaxed. Keep the bed for
sleeping.
• Wake up at the same approximate time each
morning; even on weekends and holidays.
• Avoid taking naps if you can especially after
3pm.
• Avoid any caffeine after lunch.
• Avoid reading, writing, working, eating,
watching TV, talking on the phone, or
playing cards in bed.
• Avoid cigarettes or any other source of
nicotine before bedtime.
• Make your bedroom quiet, dark and a little
bit cool. Turn your clock away from you, turn
off computers, etc.
• Clear your mind...keep a bedside journal to
jot things down that may worry you.
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Other considerations…
Rule out adrenal dysfunction, suboptimal thyroid, sleep apnea &
medications/alcohol
Melatonin 3-6 mg—taken about 6-8 PM
5-HTP 100 mg
Chamomile tea before bed
Valerian (Valeriana officinalis)(root) 400 mg
Passion Flower (Passiflora incarnata)(flower) 200 mg
Lemon Balm (Melissa officinalis)(leaves) 200 mg
German Chamomile (Matricaria recutita)(flower) 200 mg
Gamma-Amino Butyric Acid 100 mg
L-Theanine 100 mg
HPA Axis and
Adrenal Fatigue
Saliva Testing Bibliography for
Cortisol
Salivary Cortisol: A Better Measure of Adrenal Cortical Function Than
Serum. Vining RF, et al. Ann Clin Biochem (1983) 20:329-35.
Salivary Cortisol Determined by Enzyme Immunoassay is Preferable to
Serum Total Cortisol for Assessment of Dynamic Hypothalamic-PituitaryAdrenal Axis Activity. Gozansky WS, et al. Clin Endocrin (2005) 63:336-341.
Venipuncture Causes Rapid Rise in Plasma ACTH. Meeran K, et al. Br J Clin
Pract (1993) 47(5): 246-7.
Hormone Profiles in Humans Experiencing Military Survival Training.
Morgan CA, et al. Biol Psychiatry (2000) 47:891-901.
Salivary Cortisol – An Alternative to Serum Cortisol Determinations in
Dynamic Function Tests. Aardal-Eriksson E, et al. Clin Chem Lab Med (1998)
36(4):215-222.
The Role of Stress and the HPA Axis in Chronic Disease Management
Thomas Guilliams
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Fatigue in Women during
Hormonal Transitions: PMS, Post-partum,
Peri-Menopause)
A result of hormone imbalance
- Due to hormonal fluctuations
- Due to hormone declines
- Due to disrupted sleep patterns
Described as ‘crashing fatigue’
◦ When feeling of weakness, exhaustion and
reduced energy suddenly overwhelms a
woman
◦ Can come at any time; not related to exertion
and not related to being sleepy or drowsy
◦ Even after a good night’s sleep
Caused by Temporary
Hormonal Imbalance
Physical Symptoms
Mental Symptoms
- Muscle fatigue
– Decreased attention
- Sudden crashing fatigue
- Drowsiness
– Decreased wakefulness
– Apathy
– Irritability
– Memory lapses
Hutchinson, Susan MD The stages of a Woman's Life: Menstruation,
Pregnancy, Nursing, Perimenopause, Menopause Nov 2007
Love Susan MD, Menopause and Hormone Book New York Three rivers Press 2003
BMJ Group Menopause; What is it? Patient education 2007
– Trouble concentrating
Fatigue is also one of the primary
complaints with adrenal dysfunction
Very low circulating cortisol is associated with
debilitating fatigue.
People who report more nocturnal awakenings
had flatter cortisol curves.
Low morning cortisol means higher levels of
fatigue and physical symptoms later that day.
Cleare AJ. The neuroendocrinology of chronic fatigue syndrome. Endocr Rev. 2003 Apr;24(2): 236-52.
Kumari M, et al. Cortisol secretion and fatigue: associations in a community based cohort. Psychoneuroendocrinology. 2009 Nov;34(10):1476-85.
Hansen AM, et al. Salivary cortisol and sleep problems among civil servants. Psychoneuroendocrinology. 2011 Dec 29.
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Fatigue: Testing & Evaluation
Salivary hormones: Estradiol, progesterone, testosterone,
DHEA, diurnal cortisols and Melatonin
Urinary neurotransmitters: Serotonin, GABA, dopamine,
norepinephrine, epinephrine, glutamate
Initial Serum: CBC, CMP, TSH, fT3, fT4, ferritin, Vitamin D
Additional considerations: Iron study, B12, folate, thyroid antibodies
Fatigue: Treatment
Treat the cause:
Hormonal imbalance(s)
◦ Estrogen dominance: Topical progesterone with strong
consideration for oral delivery also when applicable
◦ Hypoadrenia: adaptogenic herbs, cofactor
supplementations, adrenal glandulars, cortisol
supplementation (physiologic dosing) and DHEA when
suboptimal or low
◦ Melatonin dysregulation
Treatment of ‘Fatigue’ Summary
Physiologic dosing of cortisol when indicated (see phasing and
adrenal treatment protocol )
Physiologic supplementation of DHEA
Nutrients needed for pathways; B5, B6, Vit C, Vit E
Adaptogenic Herbs
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Adaptogens
Have a normalizing effect on the body and to be capable of either toning
down or strengthening the activity of hyper and hypo functioning systems.
Antioxidant activity
Increased strength
Less craving for alcohol or sugar
Better focus and concentration
Improved blood-sugar metabolism
Improved immune resistance
Increased energy and stamina
Improved muscle tone
Better motivation and productivity
Liver protection and antitoxin activity
Faster recovery
Less anxiety
Better sleep
A feeling of well-being
Better moods
Fatigue and Neurotransmitters
Chronic Fatigue Syndrome has been shown to have an integral central
fatigue component.
“As brain function appears to be dependent upon the interaction of a
number of systems, it is unlikely that a single neurotransmitter system is
responsible for central fatigue.”
◦
◦
◦
◦
Serotonin
Dopamine
Norepinephrine & Epinephrine
Acetylcholine
Meeusen R, Watson P, Hasegawa H, Roelands B, Piacentini MF. Brain neurotransmitters in fatigue and overtraining. Appl Physiol Nutr Metab. 2007 Oct;32(5):857-64
Davis, J. M., & Bailey, S. P. (1997). Possible mechanisms of central nervous system fatigue during exercise. Medicine & Science in Sports & Exercise, 29(1), 45-57.
A Typical Treatment Plan
Adrenal support protocol –
• AM, Noon, Mid-afternoon (potentially)
• Light Therapy (similar to SAD protocol) within 30 minutes after awakening
• Rest. Bedtime goal of 7+ hours with retiring no later than 10-11pm
• Eat regular meals at regular times /and include protein at each meal
(see adrenal reset* Nutritional Plan)
• Strive for 5-7 servings of veggies and fruits daily
• Avoid: Added sugars, processed foods, ETOH
• Stress management plan: Take a look at relationships, work, lifestyle, etc. Deep
breaths throughout the day with the breath out being longer than the breath in.
• Laughter daily
• Conscious movement daily
• Can take up to six months to 2 years to resolve adrenal fatigue.
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Adrenal Reset Nutritional
Recommendations
for better sleep and optimal
adrenal revival
3 * 2 * 1 (proteins)
1*2*3
(carbohydrates)
Adrenal Summary
The role of adrenal Function is foundational for addressing
Fatigue and for individualized endocrine balancing and
hormone optimization
Since symptoms of adrenal dysfunction “sound” alike in
patients (“I’m exhausted”) – testing is mandatory for
individualization and success of treatment (Salivary testing
of four timed cortisols and DHEA levels will direct and
define treatment)
The adrenals are resilient and will usually re-calibrate and
return individuals to optimal functioning (if possible)* with
correct diagnosis and treatment within 6 months – 2 years
Charlotte, 52yo F | Cortisol series
01/2011
05/2011
2008
05/2012
09/2011
12/2012
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Weight Gain
Which has the greatest
potential to cause cancer?
Smoking cigarettes
Being overweight
Both increase risk of creating cancer….30% RISE in incidence
Belly Fat especially linked to Pancreatic, Colon, Kidney and Endometrial
Women’s Metabolism
–Hormones
–Genetics
–Lifestyle
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…the skinny on fat
Why is fat; inflammatory?
location, location, location
Because of its anatomical position, visceral fat venous blood is
drained directly to the liver through the portal vein. This
contrasts with subcutaneous fat where venous drainage is
through systemic veins. The portal drainage of visceral fat
provides direct hepatic access to FFAs and adipokines secreted
by visceral adipocytes. Adipokines activate hepatic immune
mechanisms with production of inflammatory mediators such as
C-reactive protein (CRP)
Heinrich PC, Castell JV, Andus T. Interlukin-6 and the acutephase response. Biochem J 1990; 265: 621–636.
10. Mårin P, Andersson B, Ottosson M, Olbe L, Chowdhury B,
Kvist H, Holm G, Sjöström L, Björntorp P. The morphology andmetabolism of intra-abdominal adipose tissue in men. Metabolism1992; 41: 1241–1248.
Weight Gain Considerations
•Sex hormone, adrenal, and thyroid imbalances
•Altered glucose/insulin metabolism
•Sleep dysfunction
•Poor gut health
•Slowed metabolism
•SAD lifestyle and habits
•Genetics
•Feelings of hopelessness and depleted motivations-Lifestyle
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Don’t overlook what elevated androgens
(free levels measured in saliva) mean
The connection between androgen hormones and blood
sugar regulation is crucial to recognize and identifySaliva testing of the active levels of androgen hormones
(Testosterone, DHEA, DHT) is a highly useful very
important early prognosticator of glycemic dysfunction.
Undetected, the hyperinsulinemia may progress to more
overt disease processes including insulin resistance,
metabolic syndrome and/ or diabetes.
Belly Fat and Insulin Resistance
Too many free fatty acids coming through the
portal vein in turn require the liver to produce too
much glucose.
With so much glucose, the body pumps out more
insulin to try to control the sugar’s high levels. Over
time, this contributes to insulin resistance.
Kabir M, et al. Molecular evidence supporting the portal theory:
a causative link between visceral adiposity and hepatic insulin resistance.
Am J Physiol Endocrinol Metab. 2005; 288: E454-61.
Baby Boomers and Belly Fat
On average, women gain between 12 and 15 pounds between
the ages of 45 and 55
…when menopause typically occurs.
65-80% are either obese or overweight
(10 to 30 pounds over a healthy weight)
78% of Americans not meeting basic activity level
recommendations
25% completely sedentary
NCHS
www.cdc.gov overweight and obesity
Love, Susan M.D. Dr. Susan Love’s Menopause and Hormone Book. New York: Three Rivers Press, 2003
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Body fat % change with age,
gender and menopausal status
From puberty and beyond the body fat % is greater in women than in men and is
greater in postmenopausal women (lined bar) compared with premenopausal.
Cooke PS, Naaz A. Role of estrogens in adipocyte development and function. Exp Biol Med. December 2004 229(11):1127-1135.
Postmenopausal women have higher
central body fat when compared to
premenopausal women
Gambacciani M, Cipaoni M, Cappagli B, De Simone L,
Genazzani AR. Climacteric modifications in body weight and
fat tissue distribution. Climacteric, 1999, 2, 37-44.
Tchernof A, Poehlman ET, Despres JP. Body fat distribution,
the menopause transition, and hormone replacement
therapy. Diabetes Metab. 2000 Feb;26(1):12-20.
Panotopoulos G, Raison J, Ruiz JC, Guy-Grand B, Basdevant
A. Weight gain at the time of menopause. Hum. Reprod.
1997 12(Suppl 1): 126-133.
Estrogen Regulates Adipose
Deposition
During puberty, estrogen is responsible for increase
in number of adipose cells deposited
subcutaneously.
Estrogen inhibits visceral abdominal fat in
premenopausal women by decreasing lipogenesis
in that specific area.
Cooke PS, Naaz A. Role of estrogens in adipocyte development and function. Exp Biol Med. December 2004 229(11):1127-1135.
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Estrogen and Adipose
As estrogen levels decrease,
abdominal adipose cells
increase in number as well as
size.
Estrogen replacement
(when deficient) can reverse
abdominal adipose deposition.
Haarbo J, Marslew U, Gotfredsen A, Christiansen C. Postmenopausal hormone replacement therapy prevents central distribution of body fat after
menopause. Metabolism 1991 40:1323-1326.
Mattiasson I, Rendell M, Tornquist C, Jeppsson S, Hulthen UL. Effects of estrogen replacement therapy on abdominal fat compartments as related
to glucose and lipid metabolism in early postmenopausal women. Horm Metab Res. 2002 Oct;34(10):583-8
Estrogen and Insulin
Resistance
Studies of effects of estrogen on insulin sensitivity indicate
that too little or too much estrogen contributes to insulin
resistance.
Hyperinsulinemia is a significant player in amplifying most
menopausal symptoms.
High insulin levels trigger increases in estrogen and
testosterone—vicious cycle.
Lindheim SR, Presser SC, Ditkoff EC et al. A possible bimodal effect of estrogen on insulin sensitivity in postmenopausal women
and the attenuating effect of added progestin. Fert and Steril. 1993. 60(4):664-7.
Livingstone C, Collison M. Sex steroids and insulin resistance. Clinical Science. 2002. 102(151-166).
Adipose Increases Estrogen
Adipose cells increase estrogen levels through
aromatization. The conversion of testosterone and
DHEA to estrone (E1)/estradiol (E2).
So while low E2 can contribute to weight gain, weight
gain can, in turn, contribute to E2 and E1 production.
Again…vicious cycle.
Nelson LR, Bulun SE. Estrogen production and action. J Am Acad Dermatol. 2001 Sep;45(3):S116-24.
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Progesterone & Weight Gain
Progesterone is thermogenic, it increases core temperature
and energy expenditure. It helps to burn fat for energy.
Progesterone acts as a diuretic and insufficiency leads to water
retention and bloating.
Progesterone decreases thyroid binding globulin, making
thyroid hormone more bioavailable.
Progesterone promotes good sleep—also important for weight
loss.
Lee JH. 2004
Panotopoulos G, Raison J, Ruiz JC, Guy-Grand B, Basdevant A. Weight gain at the time of menopause. Hum. Reprod. 1997 12(Suppl 1): 126-133.
Long Term Weight Loss
Success
Kraschnewski JL, Boan J, Esposito J. Int J Obes (Lond). Long-term weight loss maintenance in the United States. 2010 Nov; 34(11):1644-54.
Successful weight loss programs
have three characteristics
They educate and emphasize that weight management is a commitment to
healthy patterns/routines of exercise and eating… NOT strict dieting
alternating with carelessness about eating patterns
They are tailored to each person’s age, general health, living situation and
other individual characteristics
They recognize that the emotional, psychological and spiritual facets of
human life are equally as important to maintaining a healthy lifestyle as
medical and nutritional facets
Encyclopedia of Surgery
A guide for Caregivers
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Salivary hormone testing provides an early
warning signal of blood sugar issues
Elevated androgens – testosterone and/or DHEA
Other laboratory testing for
metabolic syndrome
•VAP (Vertical Arterial Profile)
•Clotting factors
•C-reactive protein
•Homocysteine
•Calcium Scores (CT scan)
Al-Hamodi Z, et al. Association of plasminogen activator inhibitor-1 and tissue plasminogen activator with type 2 diabetes and metabolic
syndrome in Malaysian subjects. Cardiovasc Diabetol. 2011; 10: 23.
DNA Testing for Obesity “Genes”
Gene & Role
FTO: Human fat mass and obesity associated gene
Regulation of metabolism and satiety
MC4R: Melanocortin 4 receptor
Regulation of satiation and meal frequency
ADRB2: Beta adrenergic receptors
Sensitivity to carbohydrates and stress
FABP2: Fatty Acid Binding Protein 2
Fat absorption and insulin regulation of sugar
SH2B1
Regulation of insulin and leptin systems
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Treatment benefits
Weight loss benefits:
• Improved self esteem and energy
• Improved hormone balance with decreased
androgens from decreased fat stores
• Improved SHBG levels – key in managing or preventing
metabolic syndrome
The benefits of a balanced HPA axis function:
• Improved symptoms related to inhibitory imbalances
such as sleep, mood, and pain perception
• Improved symptoms related to excitatory imbalances
such as energy, stamina, focus, and memory
Regulating menses in PCOS
Treatment options – botanical
Alternating tinctures/Westside formulas I and II
Formula I
Days 1-14
◦ (4) Cimicifuga
◦ (4) Vitex
◦ (4) Angelica
◦ (4) Medicago
◦ Sig; 1 tsp bid
Formula II
• Days 15-28
•
•
•
•
•
•
(2) Vitex
(4) Mitchella Repens
(4) Smilax
(2) Pulsatilla
(4) Dioscorea
Sig; 1 tsp bid
Erin Lommen ND 2007
Dietary approach to anovulation
Seed cycling
◦
◦
Follicular phase (days 1-14): 1-2 tablespoons of ground flax and pumpkin
Luteal phase (15-28): 1-2 tablespoons of ground sesame and sunflower seeds
Phipps WR, et al. Effect of flax seed ingestion on the menstrual cycle. J Clin Endocrinol Metab. 1993; 77: 1215-9.
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Dietary approach for IR, syndrome X
& PCOS
30-40% protein with high fiber and avoidance of starchy, sugary carbs
Abundant greens, fresh veggies…
Encourage nuts, legumes, lentils
Avoid refined processed foods, sugars and processed carbs like pasta and
breads
Avoid artificial sweeteners and sugars
• Toscani MK, et al. Effect of high-protein or normal-protein diet on weight loss, body composition, hormone and metabolic profile in women with polycystic
ovary syndrome from south brazil: a randomized study. Br J Nutr. 2005; 94: 154-65.
• Dunn N. The Natural Diet Solution for PCOS and Infertility. Seattle, WA; Health Solutions Press: 2006.
Melatonin and
Obesity
Ramin CA, et al. The association of body size in early to mid-life
with adult urinary 6-sulfatoxymelatonin levels among night shift
health care workers. BMC Public Health (2015) 15:467.
•Adult BMI is inversely associated with adult
melatonin secretion
•Night shift work did not appear to influence this
observed association.
•BMI may be an important mechanism by which
melatonin levels are altered and subsequently
influence chronic disease risk.
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Walecka-Kapica E, et al. The effect of melatonin
supplementation on the quality of sleep and weight status
in postmenopausal women. Prz Menopauzalny
2014;13(6):334-338.
The results of many experimental studies and clinical trials suggest that in the case of
obesity, the circadian and seasonal rhythm of melatonin secretion in the autumnwinter period can increase appetite and lead to weight gain. Weight gain and the
increase in the level of high-density lipoproteins was found in humans exposed to
white light at night.
Trial composed of three groups
◦
◦
◦
◦
Group I (control) – 25 women with normal body weight, without menstrual and sleep disorders.
Group II – 26 postmenopausal women with normal body weight (BMI < 24.9)
Group III -0 30 postmenopausal women with high body weight (BMI of 25.2-34.9, mean 31.2)
Women enrolled in groups II and III, in whom the weight gain occurred after menopause, and
who did not use hormones replacement therapy and felt discomfort in the form of sleep
disorders and increased appetite were included.
Women put on a standardized diet of 1500kcal and given 5mg melatonin at 21:00.
Melatonin supplementation contributed to the reduction
of body weight in obese women and after 16 weeks, BMI
decreased from 29.62to 27.88
Melatonin supplementation is justified in patients with deficiency. The
secretion of melatonin decreases with age and this process begins as early as
after 30 years of age.
It was observed that the reduction in melatonin mainly concerns
postmenopausal women; this convergence of biological processes resulted in
the introduction of the term “melatoninpause.”
The results of our studies indicate that a decrease in the activity of the
melatoninergic system particularly at night may be one of the reasons for the
tendency to gain weight in postmenopausal women.
Of note on sleep:
64% of the women in this study reported that
melatonin improved the quality of sleep from the
beginning of its administration. The remaining
patients (35%) did not feel any significant
improvement in the first month of supplementation.
This group comprised women who previously took
other hypnotic drugs. These disorders, particularly
in the form of breaks and shortening of the duration
of sleep, significantly improved after 6-8 weeks of
melatonin administration.
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Reduced fat mass and increased lean mass in response to 1
year of melatonin treatment in postmenopausal women:
A randomized placebo-controlled trial
OBJECTIVE: Apart from regulating the circadian rhythm, melatonin exerts a variety of actions in the
living organism. Among these functions, melatonin is believed to have a positive effect on body
weight and energy metabolism. So far, the evidence for this relies mainly on animal models. In this
study, we aimed to determine the effects of melatonin on body composition, lipid and glucose
metabolism in humans.
DESIGN/METHODS: In a double-blind, placebo-controlled study, we randomized 81
postmenopausal women to 1 year of treatment with melatonin (1 or 3 mg nightly) or
placebo. Body composition was measured by DXA. Measures were obtained at baseline and after 1
year of treatment along with leptin, adiponectin and insulin. Markers of glucose homeostasis were
measured at the end of the study.
RESULTS: In response to treatment, fat mass decreased in the melatonin group by 6·9%
compared to placebo. A borderline significant increase in lean mass of 5·2% was found in
the melatonin group compared to placebp. After adjusting for BMI, lean mass increased by 2·6% in
the melatonin group. Changes in body weight and BMI did not differ between groups. Adiponectin
increased borderline significantly by 21% in the melatonin group compared to placebo. No
significant changes were observed for leptin, insulin or markers of glucose homeostasis.
CONCLUSION: Our results suggest a possible beneficial effect of melatonin on body composition
and lipid metabolism as 1 year of treatment reduces fat mass, increases lean mass and is
associated with a trend towards an increase in adiponectin.
Amstrup AK, et al. Reduced fat mass and increased lean mass in response to 1 year of melatonin treatment in postmenopausal women: A
randomized placebo-controlled trial. Clin Endocrinol (Oxf) 2016 Mar;84(3):342-7.
Melatonin, Liraglutide, and Naltrexone/Bupropion for the
Treatment of Obesity and Medication-Related Weight Gain.
Overweight and obesity are associated with significant morbidity and mortality.
This is a known problem among individuals with psychiatric illness, which may be
partly due to the adverse metabolic effects of certain psychotropic drugs.
Melatonin, liraglutide, and naltrexone/bupropion are examples of drugs with
different mechanisms of action that have favorable effects on obesity or
medication-related weight gain.
Melatonin is appropriate to consider for any patient who will be started on a
psychotropic drug that is potentially associated with weight gain or other adverse
metabolic effects.
Liraglutide should also be considered appropriate for use in overweight or obese
psychiatric patients, including those with medication-associated weight gain. The
use of naltrexone/bupropion may be problematic in patients with bipolar disorder
or schizophrenia because of the potential adverse effects of the bupropion
component of the combination.
All three drugs deserve further dedicated studies in psychiatric patient populations.
Howland RH. Melatonin, Liraglutide, and Naltrexone/Bupropion for the Treatment of Obesity and Medication-Related Weight Gain. J Psychosoc Nurs
Ment Health Serv. 2015 Jun;53(6):19-22.
Short-term melatonin consumption protects the heart of obese
rats independent of body weight change and visceral adiposity.
Chronic melatonin treatment has been shown to prevent the harmful effects of dietinduced obesity and reduce myocardial susceptibility to ischaemia-reperfusion injury (IRI).
Herein, we investigated the effects of relatively short-term melatonin treatment on the
heart in a rat model of diet-induced obesity.
Control and diet-induced obese Wistar rats (fed a high calorie diet for 20 wk) were each
subdivided into three groups receiving drinking water with or without melatonin (4
mg/kg/day) for the last 6 or 3 wk of experimentation.
Diet-induced obesity caused increases in body weight gain, visceral adiposity, fasting
blood glucose, serum insulin and triglyceride (TG) levels with a concomitant cardiac
hypertrophy, large postischaemic myocardial IFSs and a reduced cardiac output.
Melatonin treatment (3 and 6 wk) decreased serum insulin levels and the HOMA index (P
< 0.05) with no effect on weight gain (after 3 wk), visceral adiposity, serum TG and glucose
levels. It increased serum adiponectin levels, reduced myocardial IFSs in both groups and
activated baseline myocardial STAT-3 and PKB/Akt, ERK42/44 and GSK-3β during
reperfusion.
Overall, short-term melatonin administration to obese/insulin resistant rats reduced
insulin resistance and protected the heart against ex vivo myocardial IRI independently
of body weight change and visceral adiposity.
Nduhirabandi F, Huisamen B, Strijdon H, Blackhurst D, Lochner A. Short-term melatonin consumption protects the heart of obese rats
independent of body weight change and visceral adiposity. J Pineal Res. 2014 Oct;57(3):317-32.
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Take home points
Adult BMI is inversely associated with melatonin secretion
Decrease in melatonin may be one reason for weight gain in
postmenopausal women
Melatonin reduced weight in diabetic and normal rats
Beneficial effect of melatonin on body composition and lipid
metabolism was observed. Melatonin supplementation reduces
fat mass, increases lean mass, and increases adiponectin
Melatonin therapy may offset the weight gain associated with
some psychotropic drugs
In obese/insulin resistant rats, melatonin reduced insulin
resistance and protected the heart.
Sleep
Leptin and Grehlin are hormones that help the body control
appetite and weight gain. Leptin suppresses appetite, while
Grehlin increases appetite and may prevent a person from
losing weight.
When lack of sleep becomes a chronic problem, levels of
Grehlin increase, causing greater appetite, and levels of
Leptin decrease. Regardless of diet and exercise, some
obesity is caused, or made worse, by sleep deprivation.
Less than 7 hours of sleep a
night? Lower BMI than <7.7
hrs a night
14.9% higher appetite stimulating hormone; ghrelin
15.5% lower leptin
6 hours; 23 % more likely to be obese
5 hrs a night; 50% more likely to be obese
2-4 hrs a night; 73% more likely to be obese
Spiegel, Karine PhD, et al. Brief Communication: Sleep Curtailment in Healthy Young Men is Associated with Decreased Leptin Levels, Elevated Ghrelin
Levels, and Increased Hunger and Appetite. Annals of Internal Medicine 7 Dec, 2004, vol 141, No. 11
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Summary
•Successful treatment strategies for weight loss employ
solutions that target and address its many causes and the
gravity of each individual case
•These programs will focus on the whole person and utilize
BHRT, Nutrition, Herbal medicine, other Supplementation,
and Lifestyle changes
•Saliva testing provides an excellent roadmap to guide your
clinical process, beginning by building a strong foundation
through balancing endocrine dysfunction
Generalized Treatment Approach
(and/or Clinical Pearls)
•Patients need to be encouraged at every visit to improve
their diets.
•Encourage good whole foods and the other (not so healthy
foods) will decrease in the diet naturally.
•Refined carbohydrates and sugar are off limits and should
be avoided!
•Eat foods that increase energy and brain function.
•Avoid foods that cause sluggishness.
•Eat regularly
•Limit Alcohol
Testing and Executive Summary for
Weight Gain
•Optimize adrenals
•Balance sex hormones: Estrogens, progesterone and
androgens (testosterone and DHEA)
•Improve sleep quality
•Identify genetic tendencies
•Treat the individual-and avoid triggering deprivation
response
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IBS
IBS
“Irritable bowel syndrome (IBS) is a common intestinal
condition characterized by abdominal pain and cramps;
changes in bowel movements (diarrhea, constipation, or both);
flatulence; bloating; nausea; and other symptoms. The cause is
unknown. There is no cure for IBS*. Much about the condition
remains unknown or poorly understood; however, dietary
changes, drugs, and psychological treatment are often able to
eliminate or substantially reduce its symptoms”.
Medical Dictionary by Farlex
And How Do These Patients
Present?
•Pain
•Constipation
•Gas
•Rectal irritation
•Bloating
•No appetite
•Insomnia
•Reflux
•Fatigue
and sometimes
•“Everything’s fine”
•Foul-smelling stool
•Diarrhea
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“GI Health” Impacts Systemic Health
Hippocrates 400 BC
“Death sits in the bowels,” and “bad digestion is the root of
all evil.”
Jeremy Nicholson, PhD 2013
“Almost every sort of disease has a gut bug connection”
Hypertension, Cardiovascular disease, Diabetes, Autoimmunity,
Inflammation, Asthma/Eczema, Depression/Anxiety/ASD
Sci Transl Med (2013)5(172):172ra22 DOI: 10.1126/scitranslmed.3005114
3
The Gastrointestinal (GI) Ecosystem
Microbiome = Microbiota plus their genetic material
Metabolome = Microbiome plus it’s collective metabolites
Microbial Metabolites- intermediary and final compounds,
including cellular constituents (lipopolysaccharides)
positive or negative
GUT
SYSTEMICALLY
CNS
Cover your bases…
• Approaches for assessing the patient’s microbiota
• Rapid detection of 22 common pathogenic bacteria,
parasites and viruses
• The GI microbiome as a huge player in detoxification
• The microbiome and inflammation (Nrf2 and NF-ҡB)
5
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GI Inflammation Impairs Innate Detoxification
Intestinal inflammation down-regulates hepatic efflux pump
activity
Accumulation of Phases II and I
increases oxidative stress
Clinically- Check
Levels of inflammatory protein biomarkers in stool
Dysbiotic gram negative bacteria (K. pneumoniae, P. aeruginosa)
Beneficial bacteria (integrity of the mucus and mucosal barriers)
Vitamin D (dampens pro-inflammatory cytokine response)
sIgA- immunoglobulin with anti-inflammatory effects
(S. boulardii, Lactobacillus rhamnosus GG, Bifidobacterium lactis Bb-12)
Toxicol Sci(2009)107:27-39 Am J Physiol(2007)292:G1114-22 JBC(2006)281:17883-89 Gastroenterol(2008)135:529-38
Immunity(2007)26:812-26
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Etiology Of Small Intestinal
Bacterial Overgrowth (SIBO)
Normal gut microflora is maintained by 4
major mechanisms:
◦ gastric acid secretion,
◦ pancreatic enzyme secretion,
◦ small intestinal motility
◦ structural integrity of the GI tract
Contributing Factors Of GI
Diseases; Lifestyle Choices
High intake of carbohydrates …
High intake of sugar
High intake of animal protein
Hydrogenated oils…
Alcohol
Nicotine
Caffeine
Artificial sweeteners
Antibiotics
Pain medications
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Modalities For Treatment
•Dietary intervention
•Lifestyle changes
•Nutrient and probiotic supplementation
•Botanical medicine
•IV nutriceuticals
•Hormones (BHRT)
•Rx
IBS/Food Allergies
Consider in patients with symptoms:
◦ Abd pain, bloating, constipation, diarrhea
Also consider in asymptomatic patients (ie: no GI
complaints) not responding to treatment
Start with probiotics and modified elimination diet
◦ Severe adrenal fatigue patients are typically unable to
make many changes in the beginning
◦ Consider meal replacement shakes for 1 meal a day
Microbiome and Hormones
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Treatment for IBS
Clinical Pearls and
Resources
More than hormones:
neurotransmitters and hot flashes
•Declining estrogen levels decrease serotonin receptor
sensitivity, contributing to temperature regulation
changes and hot flashes.
•Partial explanation of
why SSRIs are being
marketed to participate
in helping alleviate hot
flashes for women
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Cortisol Levels & Thyroid
Function
Dysregulation of cortisol affects thyroid hormone
production, conversion & receptor uptake:
◦ Adrenal fatigue decreases type 1 deiodinase and T4
cannot convert as readily to T3
◦ Adrenal fatigue down regulates T3 receptors and
decreases T3 uptake from cells
◦ During stress: Hypothalamic CRH inhibits GnRH and via
somatostatin inhibits hGH, TRH and TSH secretion
suppressing reproduction, growth and thyroid function.
Common Misnomers and
Misconceptions
•There is no such thing as Adrenal Fatigue (as it were)- the gland itself does
not stop producing cortisol…rather HPA axis adaptations occur due chronic
demands due to stressors (allostatic load)
•No direct feedback between zona
fasciculata and zona reticularis-treat
each zone as if separate gland…
•Treat the ‘pathway’ as well as the level
•Treat HPA dysfunction first…then may need to treat Hypoadrenia if present
•Melatonin, phosphorylated serine and even DHEA, can be used to quiet
erratic HPA activity
•ACTH is preferentially stimulating increased androgen secretion (rather than
cortisol) in some women with metabolic syndrome and PCOS
Lavender
Hirokawa K, Nishimoto T, Taniguchi T. Effects of lavender aroma on sleep quality
in healthy Japanese students. Perceptual and Motor Skills 2012;114:111-22.
Lewith GT, Godfrey AD, Prescott P. A single-blinded, randomized pilot study
evaluating the aroma of Lavandula augustifolia as a treatment for mild
insomnia. J Altern Complement Med 2005;11:631-7.
Morris N. The effects of lavender (Lavendula angustifolium) baths on
psychological well-being: two exploratory randomised control trials.
Complement Ther Med 2002;10:223-8.
Akhondzadeh S, Kashani L, Fotouhi A, et al. Comparison of Lavandula
angustifolia Mill. tincture and imipramine in the treatment of mild to moderate
depression: a double-blind, randomized trial. Prog Neuropsychopharmacol Biol
Psychiatry 2003;27:123-7
Buckle J. Use of aromatherapy as a complementary treatment for chronic pain.
Altern Ther Health Med 1999;5:42-51.
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Executive Summary of Treatment
for top complaints of Menopause
•Don’t guess: TEST
•Most --if not all complaints can be addressed utilizing
lifestyle, nutrition, botanicals and BHRT
•Begin by balancing foundational systems (Hormones,
Adrenals, Gut, Thyroid) and conservatively addressing
hormone levels when deficiencies exist
•Remember the Neuroendocrine aspect of Menopause and
include NT (neurotransmitter) testing where applicable
…“show me a day when
the world was not new”
Barbara Hence
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