PMS and PCOS - Genova Diagnostics

Balancing Younger Women’s Hormones
PMS, PCOS and Infertility
Pamela W. Smith, M.D., MPH, MS
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Christine Stubbe, ND
Medical Education Specialist - Asheville
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Pamela W. Smith, M.D., MPH, MS
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Balancing Younger Women’s Hormones
PMS, PCOS and Infertility
Pamela W. Smith, M.D., MPH, MS
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7
Additional Information
•
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Join us for the Fellowship/Master's Degree in Metabolic and Nutritional Medicine. Each of the
modules/courses are offered in conjunction with The University of South Florida Morsani College of
Medicine
Open to MDs/DOs, Pharmacists, PAs, NPs, NDs, PhDs, DCs, DDSs, CCNs and anyone else who takes
care of patients.
Module I: A Metabolic/Functional Medicine Approach to Hormone Replacement Therapy, Adrenals,
and Hypothyroidism
Module II: A Metabolic/Functional Medicine Approach to Hypercholesterolemia, Hypertension and
Insulin Resistance/Diabetes
Module III: A Metabolic/Functional Medicine Approach to GI Health, Neurology and
Neurotransmitters
Module IV: Nutritional Depletions Caused by Medications, Amino Acids, Fatty Acids and Liver
Detoxification
Module V: Clinical Intensives: Numerous Case Histories of Hundreds of Patients from a
Metabolic/Functional Medicine Approach
Join us on-line or in person. The modules in person are rotated around the U.S. and module V is
also offered in the U.S. and overseas.
For more information on these educational experiences and 40 other modules that are offered
please contact me at: pepper4@sbcglobal.net
Pamela Smith, M.D., MPH, MS. Co-Director, Master's Program in Medical Sciences with a
concentration in Metabolic and Nutritional Medicine, Morsani College of Medicine University of
South Florida.
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Reference
– Smith, P., What You Must Know About Women’s Hormones, Garden
City Park, NY: Square One Publishing, 2009.
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PMS
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PMS
• PMS is a hormonal disorder characterized by the monthly
recurrence of certain physical or psychological symptoms
during the two weeks before menstruation and the subsiding
of those symptoms when flow begins or slightly afterwards.
11
Common PMS Symptoms
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Abdominal bloating
Acne
Angry outbursts
Anxiety
Appetite changes
Asthmatic attacks
Avoidance of social activities
Backache
Bladder irritation
12
Common PMS Symptoms (Cont.)
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Bleeding gums
Breast swelling/tenderness
Bruising
Clumsiness
Confusion
Conjunctivitis
Constipation
Cramps
Craving salty foods or sweets
13
Common PMS Symptoms (Cont.)
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Crying spells
Decreased hearing
Decreased productivity
Decreased sex drive
Depression
Distractibility
Dizziness
Drowsiness
Eye Pain
14
Common PMS Symptoms (Cont.)
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Facial swelling
Fatigue
Fear of going out alone
Fear of losing control
Finger swelling
Food sensitivity
Forgetfulness
Aches and pains
Headaches
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Common PMS Symptoms (Cont.)
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Herpetic outbreak
Hives or rashes
Hot flashes
Alcohol sensitivity
Sensitivity to light and noise
Inefficiency
Indecision
Insomnia
Irritability
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Common PMS Symptoms (Cont.)
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Joint pains
Leg cramps
Leg swelling
Mood swings
Nausea
Palpitations
Panic attacks
Poor coordination
Poor judgment
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Common PMS Symptoms (Cont.)
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Poor memory
Poor vision
Restlessness
Ringing in ears
Runny nose
Seizures
Sinusitis
Sore throat
Spots in front of eyes
18
Common PMS Symptoms (Cont.)
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Suspiciousness
Tearfulness
Tension
Tingling in hands and feet
Tremors
Visual changes
Vomiting
Weight gain
19
PMS is Frequently Misdiagnosed as a
Psychological Problem
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Anxiety disorder
Depression
Seizure disorder
Panic attacks
Agoraphobia
Eating disorders
Various personality disorders
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PMS
• Can be treated with a better than 90% success rate.
• There is no definitive diagnostic test that confirms a diagnosis
of PMS.
• There is no clear course of development. However, something
in the patients lives interferes with the pituitary-ovarian
feedback loop, and it decreases the supply of progesterone.
21
Precipitating Factors For PMS
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Oral contraceptives due to progestin
Pregnancies
Miscarriages and abortions
Tubal ligations
– 37% of women who have a tubal ligation develop PMS and other
complications such as pelvic pain and irregular cycles.
– Studies have shown that after tubal ligation women have higher
estrogen and lower progesterone levels in the second half of their
cycles.
22
Precipitating Factors For PMS (Cont.)
• Partial hysterectomy
– Even in patients who never had PMS before due to the decreased
supply of blood to the ovaries post hysterectomy
• Age
23
Key Factor
• Low blood sugar
– Due to hormonal changes a woman’s body becomes more sensitized
to drops in blood sugar the last two weeks of the cycle
– Symptoms of hypoglycemia are very much like PMS symptoms
– Treatment
• 6 small meals a day
• No refined sugars
• B6 which is needed for the production of dopamine and serotonin (Use B
complex)
• Avoid caffeine and alcohol who are antagonist to B vitamins
24
Caffeine
• Caffeine makes things worse
– Increases the body’s production of prostaglandins which increase
during the premenstrual period and can cause breast tenderness,
arthritis, abdominal cramping, headaches and backaches
– Acts as a diuretic which depletes the body of potassium, magnesium,
B and C vitamins
– Causes the release of adrenalin which can lower blood sugar
25
Migraine Headaches
• Hormonally related migraines—Test:
– Did the headaches have their onset at puberty, or after first taking
contraceptive pills, or after a pregnancy?
– Did the attacks occur at the same time of each cycle?
– Free from headaches during the later states of pregnancy?
– Increases in severity of headaches after each pregnancy, abortion or
miscarriage?
26
Four Main Mechanisms of Hormonally
Related Headaches
• Estrogen and progesterone increase at the time of ovulation.
This can precipitate a headache. Estrogen binds salt in the
body which may cause edema including swelling of the tissues
in the brain.
• Hypoglycemia
• Changing estrogen levels
• Estrogen dominance
27
Edema
• Avoid foods with high sodium content
• Incorporate foods into the diet that are natural diuretics like
strawberries and parsley
• Use evening primrose oil (500-3,000 mg qd)
• Increase water intake
• Exercise
• Use progesterone which is a natural diuretic
• Try not to use prescription diuretics
– Use spironolactone using a prescription diuretic
28
Magnesium
• Women with PMS have low magnesium levels
– Eat foods high in magnesium
– Take magnesium supplements (400-600 mg)
29
Vitamin A
• Has been shown to relieve PMS symptoms
– Is a diuretic
– Combats stress and fatigue
– Is an antioxidant
30
Exercise
• Exercise helps with PMS symptoms
– Helps relieve painful muscles and joints, tension headaches, low back
pain, lower body bloating, tiredness, and irritability
31
Herbal Therapies
• Black Cohosh (Cimicifuga racemosa/Actaea racemosa)
–
–
–
–
Has a balancing affect on estrogen
Relaxant
Sedative
Anti-spasmotic
• Chasteberry (Vitex agnus castus)
– Decreases LH and prolactin
– Raises progesterone and facilitates progesterone function
– Acts as a diuretic
• Murray, M., The healing Power of Herbs. California: Prima Publications,
1995, p. 375.
32
Progesterone
• Very effective in treating PMS
– Use days 14-25 of cycle
33
PCOS
34
PCOS
• Affects nearly 10% of the women in the U.S.
• Accounts for 75% of the women with amenorrhea
• Accounts for 85% of women with androgen excess and
hirsutism.
– Marchese, M., “Environmental medicine update,” Townsend Letter
Feb/March 2012; p. 66-8.
– Guzick, D., “Polycystic ovarian syndrome,” Obstet Gynecol 2004;
103(1):181-93.
35
PCOS (Cont.)
• Consensus workshop sponsored by the European Society of
Human Reproduction and Embryology (ESHRE) and the
American Society of Reproductive Medicine (ASRM) in 2003
agreed upon a new definition of PCOS.
36
PCOS (Cont.)
• Two out of three criteria must be present
– Oligoovulation and/or anovulation
– Clinical or biochemical signs of excess androgen activity
– Polycystic ovaries on ultrasound (> or equal 12 follicles 2-9 mm or vol >
10 ml)
• Alexander, C., “Polycystic ovary syndrome: a major unrecognized
cardiovascular risk factor in women,” Rev Obstet Gynecol 2009; 2(4):23239.
• Ibid., Marchese.
37
Signs and Symptoms of PCOS
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Obesity
Irregular or absent menstrual cycles
Infertility/recurrent miscarriage
Hirsutism
Oily skin/acne
Alopecia
Acrochordons (skin tags)
Depression
– Ahene, S., et al., “Polycystic ovary syndrome,” Nurs Stand 2004;
18(26):40-4.
38
Signs and Symptoms of PCOS (Cont.)
• 40% of hirsute women who have normal cycles are
anovulatory.
– Ibid., Marchese.
– Carmina, E., “Diagnosing PCOS in women who menstruate regularly,”
Contemp Obstet Gynecol 2003; 53-64.
39
Signs and Symptoms of PCOS (Cont.)
• Hirsutism and acne are present in 70% of women with PCOS
and 10% of women without PCOS.
– Ibid., Marchese.
– Hill, K., “Update: the pathogenesis and treatment of PCOS,” Nurse
Pract 2003; 28:8-25.
40
Signs and Symptoms of PCOS (Cont.)
• Infertility affects 75% of women that are obese with PCOS.
• Weight gain is usually around the waist as opposed to overall
weight gain.
– Ibid., Marchese.
– Pritts, E., “Treatment of the infertile woman with polycystic ovarian
syndrome,” Obstet Gynecol Surv 2002; 57:587-97.
41
Signs/Symptoms That Are Revealed
Through Lab Results or Other Tests
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Cysts on the ovaries
High testosterone level
Elevated insulin level/insulin resistance
Elevated LH
Decreased SHBG
Abnormal lipid profile
Hypertension
42
Causes of PCOS
• Many scientist believe that PCOS has a hereditary component.
– Atimo, W., et al., “Familial ssociations in women with polycystic ovary
syndrome,” Fert Steril 2003; 80(1):143-45.
– Gonzalez, C., et al., “Polycystic ovaries in childhood: a common finding
in daughters of PCOS patients of PCOS patients. A pilot study,” Hum
Repro 2002; 17(3):771-76.
43
Causes of PCOS (Cont.)
• There is some suggestion in the medical literature that women
with PCOS are born with a gene that triggers higher than
normal levels of androgen or insulin.
– Strauss, J., et al., “Some new thoughts on the pathophysiology and
genetics of polycystic ovary syndrome,” Ann NY Acd Sci 2003; 997:42-8.
– Carey, A., et al., “Evidence for a single gene effect causing polycystic
ovaries and male pattern baldness,” Clin Endocrinol 38(6):653-8.
44
Causes of PCOS (Cont.)
• Studies have shown that the high levels of testosterone and
insulin in patients with PCOS are linked.
• This link is a gene called follistatin.
• Functions of follistatin
– Plays a role in the development of the ovaries
– Is needed to make insulin
• Urbanek, M., et al., Thirty seven candidate genes for PCOS: Strongest
evidence of linkage is follistatin,” Proc Nat Acd Sci 1999; 38(6):653-58.
45
Causes of PCOS (Cont.)
• Women that are overweight and women that are not that
have PCOS, both have a higher rate of insulin resistance and
hyperinsulinemia than controls.
– King, J., “Polycystic ovarian syndrome,” Jour Midwifery Women’s
Health 2006; 51(6):415-22.
46
Causes of PCOS (Cont.)
• Insulin decreases SHBG levels which increases the level of
circulating testosterone.
– Ibid., King.
– Ibid., Tsilchorozidou.
• Insulin works with LH to increase androgen production in the
ovarian theca cells.
– Ibid., Marchese.
47
Causes of PCOS (Cont.)
• Women with PCOS have an increase in LH amplitude and
frequency which results in an elevated 24-hour secretion of LH.
– Ibid., Marchese.
• Increased LH levels leads to an increase in androgen production
by the theca cells in the ovary.
– Ibid., Marchese.
48
Causes of PCOS (Cont.)
• Defect in androgen production resulting in increased ovarian
androgen production.
• Due to an increase in ovarian enzymatic activity involved in
the making of testosterone precursors which leads to elevated
testosterone levels.
– Ibid., Marchese.
– Ibid., King.
– Ibid., Tsilchorozidou.
49
Causes of PCOS (Cont.)
• Phthalates, bisphenol-A, cadmium, and mercury toxicities
have all be related to PCOS.
– Altering hormones to cause anovulation
– Development of insulin resistance
– Hyperandrogenemia
• Ibid., Marchese.
50
Causes of PCOS (Cont.)
• Stress may be a contributing factor to PCOS.
– Marantides, D., et al., “Management of polycystic ovary syndrome,”
Nurse Pract 1997; 22(12):34-8, 40-1.
51
Stress and PCOS
• Studies have shown that many women with PCOS cannot
process cortisol effectively, leading to elevated cortisol levels
in the body.
– Tsilchorozidou, T., et al., “Altered cortisol metabolism in polycystic
ovary syndrome: insulin enhances 5 alpha-reduction but not the
elevated adrenal steroid production rates,” Jour Clin Endocrino Metab
2003; 88(12):5907-13.
52
Stress and PCOS (Cont.)
• When women are under stress, too much prolactin may be
released. This may affect the ability of the ovaries to produce
the right balance of hormones.
– Barnea, E., et al., “Stress-related reproductive failure,” Jour IVF
Embryo Transfer 1991; 8:15-23.
– Ibid., King.
– Tsilchorozidou, T., et al., “The pathophysiology of polycystic ovarian
syndrome,” Clin Endocrinol (Oxf) 2004; 60:1-17.
53
Differential Diagnosis for PCOS
• Differential diagnosis of other disease states with polycysticappearing ovaries
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–
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Hypothyroidism
Hypothalamic amenorrhea
Cushing’s syndrome
Congenital adrenal hyperplasia
Ovarian/adrenal tumors
54
References
– Ibid., Marchese.
– Chang, R., et al., Normal ovulatory women with polycystic ovaries have
hypoandrogenic pituitary-ovarian responses to gonadotropin-releasing
hormone-agonist testing,” Jour Clin Endocrinol Metab 2000; 85(3):9951000.
55
PCOS: Risk Factor For Other Major Diseases
• Diabetes
– Pelusi, B., et al., “Type 2 diabetes and the polycystic ovary syndrome,”
Minerva Ginecol 2004; 56(1):41-51.
• Heart Disease
– Talbott, E., et al., “Cardiovascular risk in women with polycystic ovary
syndrome,” Obstet Gynedol Clin North Amer 2001; 28(1):111-33.
• Hypertension
– Rajkhowa, M., et al., “Polycystic ovary syndrome: a risk for
cardiovascular disease,” BJOG: Int Jour Obstet Bynecol 2000;
107(1):11-8.
56
PCOS: Risk Factor For Other Major Diseases
(Cont.)
• Infertility
– Trent, M., et al. “Fertility concerns and sexual behavior in adolescent
girls with polycystic ovary syndrome: implications for quality of life,”
Jour Pedatr Sdolesc Gynecol 2003; 16(1):33-7.
• Hormonally related cancers
– Radulovic, A., et al., “Obesity and hormone function changes in female
patients with polycystic ovaries,” Med Pregl 2003; 56(9-10):476-80.
• Obesity
– Gonzalez, C., et al., “Polycystic ovarian disease: clinical and
biochemical expression,” Ginecol Obstet Mex 2003; 71:253-58.
57
Diabetes and PCOS
• PCOS is a risk factor for diabetes.
– Pelusi, B., et al., “Type 2 diabetes and the polycystic ovary syndrome,”
Minerva Ginecol 2004; 56(1):41-51.
• If the patient has PCOS they are seven times more likely to get
diabetes.
– Legro, R., et al., “Prevalence and predictors of risk for Type 2 diabetes
mellitus and impaired glucose tolerance in polycystic ovary syndrome:
a prospective, controlled study in 254 affected women,” Jour Clin
Endocrinol Metabol 1999; 84(1):165-69.
• About half of all women with PCOS have insulin resistance.
– De Leo, V., et al., “Polycystic ovary syndrome and type 2 diabetes
mellitus,” Minera Ginecol 2004; 56(1):53-62.
58
Diabetes and PCOS (Cont.)
• Some studies suggest that women with PCOS who have
irregular cycles or no cycles may have double the risk for
diabetes.
• Solomon, C., et al., “Long or irregular menstrual cycle as a marker for the
risk of type 2 diabetes mellitus,” JAMA 2001; 286(19):2421-26.
• Risk factor for diabetes in patients with an irregular cycle
increases even more if the patient is obese.
• Ibid., Solomon.
59
Diabetes and PCOS (Cont.)
• The risk of getting diabetes is also increased in patients with
PCOS that are not overweight or insulin resistant.
– Danaif, A., et al., “Beta cell dysfunction independent of obesity and
glucose intolerance in the polycystic ovary syndrome,” Jour Clin
Endocrinol Metab 1996; 81:942-47.
60
Heart Disease and PCOS
• Women with PCOS have an increased risk of heart disease
compared to women without PCOS.
– Christian, R., et al., “Prevalence and predictors of coronary artery
calcification in women with polycystic ovary syndrome,” Jour Clin
Endocrinol Metab 2003; 88(6):2562-68.
– Wild, S., et al., “Cardiovascular disease in women with PCOS: A longterm follow up: A retrospective cohort study,” Clin Endocrinol (Oxf)
2000; 52(5):595-600.
– Talbot, E., et al., “Cardiovascular risk in women with polycystic ovary
syndrome,” Obstet Gynecol Clin North Amer 2001; 28(1):111-33.
61
Heart Disease and PCOS (Cont.)
• Up to 70% of women in the U.S. with PCOS have dyslipidemia.
• Ibid., Marchese.
• Women with PCOS frequently have elevated LDL.
• Orio, F., et al., “The cardiovascular risk of young women wit polycystic
ovary syndrome: an observational, analytical, prospective case-control
study,” Jour Clin Endocrinol Metab 2004; 89(8):3696-701.
• Ibid., Marchese.
• Chang, R., “A practical approach to the diagnosis of polycystic ovary
syndrome,” Amer Jour Obstet Gynecol 2004; 101:713-17.
62
References (Cont.)
– Wild, R., et al., “Assessment of cardiovascular risk and prevention of
cardiovascular disease in women with the polycystic syndrome: a
consensus statement by the Androgen Excess and Polycystic Ovary
Syndrome (AE-PCOS) society,” Fertil Steril 20011; 95(3):1073-79.
– Ehrmann, D., “Polycystic ovarian syndrome,” NEJM 2005; 353:1223-36.
– Phelan, N., et al., “Lipoprotein subclass patterns in women with
polycystic ovary syndrome (PCOS) compared with equally insulinresistant women without PCOS; Jour Clin Endocrinol Metab 2010;
95(8):3933-39.
63
Heart Disease and PCOS
• Homocysteine levels are increased in patients with PCOS.
– Loverro, G., et al., “The plasma homocysteine levels are increased in
polycystic ovary syndrome,” Gynecol Obstet Invest 2002; 53(3):157-62.
64
Heart Disease and PCOS (Cont.)
• Women with PCOS have a higher than usual rate of elevated
CRP.
– Boulman, N., et al., “Increased C-reactive protein levels in the
polycystic ovary syndrome: a marker of cardiovascular disease,” Jour
Clin Endocrinol Metabol 2004; 89(5):2160-65.
65
Heart Disease and PCOS (Cont.)
• Women with PCOS frequently have decreased total
antioxidant status and increased oxidative stress.
• This pattern may be one of the contributing causes of heart
disease in women with PCOS.
• Fenkev, I., et al., “Decreased total antioxidant status and increased
oxidative stress in women with polycystic ovary syndrome may contribute
to the risk of cardiovascular disease,” Fertil Steril 2003; 8091):123-27.
66
Hypertension and PCOS
• Women with PCOS have four times the rate of hypertension
than women who do not have PCOS.
– Lefebvre, P., et al., “Long-term risks of polycystic ovaries syndrome,”
Gynecol Obstet Fertil 2004; 32(3):193-98.
67
Hypertension and PCOS (Cont.)
• Insulin resistance and hyperinsulinemia raise blood pressure.
– Landsberg, M., “Insulin sensitivity in the pathogenesis of hypertension
and hypertensive complications,” Clin and Experimental Hyper 1996;
18(3-4):337-46.
68
Hypertension and PCOS (Cont.)
How Hyperinsulinemia Causes HTN
• High levels of insulin correlate with low sodium in the urine.
• This leads to an increase in water retention which makes it
harder for blood to flow through the circulatory system.
• Consequently leading to an increase in blood pressure.
• Insulin also elevates blood pressure by affecting the elasticity
of arterial walls.
69
Hypertension and PCOS (Cont.)
How Hyperinsulinemia Causes HTN
• Insulin alters the mechanical action of the blood vessel walls
by acting on smooth muscle cells stimulating them and
making them larger.
• As smooth muscle cells grow, they make the arterial walls
thicker, stiffer, and less supple. This forces the heart to work
harder and exert more pressure to force the blood through
the narrowed vessels.
70
Infertility and PCOS
• In women with PCOS, the ovarian follicles start to mature but
fail to ripen or to be released.
• They stay in the ovaries and continue to produce estrogen,
but no progesterone.
• Elevated levels of LH and estrogen have been found in some
women with PCOS. This may block ovulation.
– Milsom, S., et al., “LH levels in women with polycystic ovarian
syndrome: have modern assays made them irrelevant? British Journ of
Obstec and Gynecol 2003; 110(8):760-4.
71
Infertility and PCOS (Cont.)
• Higher than normal levels of testosterone are also found in
PCOS patients. High levels of testosterone inhibits ovulation.
– Franks, S., “The ubiquituous polycystic ovary,” Jour Endocrinol 1991;
129:317-19.
• Women with PCOS may miscarry at a higher rate than women
without PCOS.
– Diejomaoh, M., et al., “The relationship of recurrent spontaneous
miscarriage with reporductive failure, “ Med Princ Pract 2003;
12(2):107-11.
– Rai, R., et al., “Polycystic ovaries and recurrent miscarriage—a
reappraisal,” Hum Repro 2000; 15:612-15.
72
Infertility and PCOS (Cont.)
• Insulin also plays a role in ovulation
• The ovaries have insulin receptors
• Insulin stimulates an increase in LH and androgen levels
decreasing SHBG
• In the presence of elevated androgens, LH levels increase and
lead to poor follicle development and failure to ovulate.
73
PCOS and Hormonally Related Cancers
• Women who had a history of PCOS and irregular periods have
a five-fold increase in endometrial cancer.
• Hardiman, P., et al., “Polycystic ovary syndrome and endometrial
carcinoma, Lancet 2003; 361(9371):1810-12.
• Women who have a history of PCOS may have an increased
risk of ovarian cancer.
• Spremovi, R., et al., “The polycystic ovary syndrome associated with
ovarian tumor,” Srp Arh Celok Lek 1997; 125 (11-12):375-77.
74
PCOS and Hormonally Related Cancers
(Cont.)
• Women with a history of PCOS may be at risk for breast
cancer since they tend to be over weight and have hormonal
changes that can lead to unopposed estrogen in the body.
– Wild, S., et al., “Long-term consequences of polycystic ovary
syndrome: results of a 31-year study,” Hum Fertil (Camb) 2000;
3(2):101-05.
75
Obesity
• Studies have shown that women with PCOS store fat better
and burn calories at a slower rate than women who do not
have PCOS.
– Robinson, S., et al., “Postprandial thermogenesis is reduced in
polycystic ovary syndrome and is associated with increased insulin
resistance,” Clin Endocrinol (Oxf) 1992; 36(6):537-43.
– Faloia, E., et al., “Body composition, fat distribution and metabolic
characteristics in lean and obese women with polycystic ovary
syndrome,” Jour Endocrinol Invest 2004; 27(5):424-29.
– Gambineri, A., et al., “Obesity and the polycystic ovary syndrome,” Int
Jour Obes Relat Metab Disord 2002; 26(7):883-96.
76
Treatment of PCOS
•
•
•
•
•
•
•
•
•
Medications
Fiber
Low GI program
Reduce stress
Essential fatty acids
Drink enough water
Antioxidants
Herbal remedies
Detoxification
77
Medications
• Anti-androgen medications
– Aldactone (spironolactone)
– Tagament (cimetidine)
• Testosterone metabolism blockers
– Propecia (finsteride)
• Medications to lower blood sugar
– Glucophage (metformin) is the most successful
• Gonadotropin-Releasing Hormone Antagonists
– Lupron (leuprolide)
78
Medications (Cont.)
• Hair growth stimulators
– Rogaine solution (minoxidil)
• Hair metabolism inhibitors
– Vaniqa cream (eflornithine)
• Menstrual Regulators
– Progestins
– BCP
• Choose ones that are the least androgenic (desogestrel or norgestimate)
– Progesterone
79
Medications (Cont.) and Surgical Treatment
of PCOS
• Ovulation Inducers
–
–
–
–
Clomid/Serophene (clomiphene)
Pergonal/Humegon/Repronex (hMG)
Follistim/Gonal (FSH)
Profasi/Pregnyl (HCG)
• Surgery
– Ovarian wedge resection
– Laparoscopic ovarian drilling
80
Fiber
• Fiber lowers blood sugar, blood pressure and cholesterol.
– Anderson, J., et al., “Dietary fiber: diabetes and obesity,” Amer Jour
Gasteroenterol 1986; 81:898-906.
– Burke, V., “Dietary protein and soluble fiber reduce ambulatory blood
pressure in treatment of hypertensives,” Hypertension 2001;
38(4):821-26.
– Anderson, J., et al., “High-fiber diets for diabetic and
hypertriglyceridemic patients,” Can Med Assoc Jour 1980; 123:975.
– Sprecher, d., et al., “efficacy of psyllium in reducing serum cholesterol
levels in hypercholesterolemic patietns on high-or low-fat diets,” Ann
Inter Med 1993; 119:545-54.
81
Low Glycemic Index Diet, Weight Loss, and
Exercise
• Place the PCOS patient on a low glycemic index eating
program along with moderate exercise.
• Study done with 18 women with PCOS involved a 6 month
weight loss program and exercise.
82
Low Glycemic Index Diet, Weight Loss, and
Exercise
• Study revealed the following results
–
–
–
–
–
11% reduction in central fat
71% improvement in insulin sensitivity index
33% decrease in fasting insulin levels
39% decrease in LH levels
50% of the women started ovulating
• Huber-Buchholz, M., et al., “Restoration of reproductive potential by
lifestyle modification in obese polycystic ovary syndrome: role of insulin
sensitivity and luteinizing hormone,” Jour Clin Endocrinol Metab 1999;
84(4):1470-74.
83
Reduce Stress
• Cortisol stimulates the release of glucose, fats, and amino
acids for the production of energy in the body.
• During times of stress, cortisol and insulin levels rise in the
body. Cholesterol levels may rise as well.
• If cortisol is increased it decreases the making of
progesterone and its activity. Cortisol competes with
progesterone for common receptors.
– Bland, J., “Introduction to neuroendocrine disorders,” Functional
Medicine Approaches to Endocrine Disturbances of Aging. Gig Harbor,
Washington: The Functional medicine Institute, 2001; p. 121.
84
Reduce Stress (Cont.)
• Consequently, if cortisol levels are elevated, the symptoms of
PCOS can be exacerbated.
85
Essential Fatty Acids
• Essential fatty acids slow down the absorption of
carbohydrates into the blood stream.
– Kasim Karakas, M., et al., “Metabolic and endocrine effects of a
polyunsaturated fatty acid-rich diet in polycystic ovary syndrome,” Jour
Clin Endocrinol Metabol 2004; 89(2):615-20.
86
Drink Enough Water
• The amount of water the body needs in one day is: 1/2 the
body weight in oz. every day.
• People who drink 5 to 8 glasses of water a day have fewer
heart attacks. Dehydration increases the tendency for the
blood.
– Chan, J., et al., “Water, other fluids, and fatal coronary heart disease,”
Amer Jour Epidemiol 2002; 155(9):827-33.
87
Nutritional Treatment of Insulin Resistance
• Chromium picolinate (400-600 micrograms)
– Decreases sugar cravings and improves insulin sensitivity
• Lipoic acid (200-600 mg)
– Improves insulin sensitivity and helps prevent neuropathy
• CLA (1,000-3,000 mg)
– Improves insulin sensitivity
• Zinc 25-50 mg)
– Helps balance blood sugar levels
• Vitamin E (600-800 IU natural)
– Helps balance hormonal function
88
Nutritional Treatment of Insulin Resistance
• Taurine (1,000-3,000 mg)
– Increases activity of insulin receptor and improves sensitivity to insulin
• Magnesium (400-800 mg)
– Improves glucose uptake
• Biotin (4-8 mg)
– Increases insulin sensitivity
• Vanadium (20-50 mg)
– Improves insulin sensitivity
• Vitamin D (400-2,000 IU)
– Helps pancreas release insulin
89
Nutritional Treatment of Insulin Resistance
• Co-enzyme Q-10 (30-300 mg)
– Provides energy for metabolic pathways
• B complex (50-100 mg)
– Aids in glucose metabolism and decreases sugar cravings
• Vitamin C (1,000-3,000 mg)
– Cofactor in glucose metabolism
• Manganese (5-10 mg)
– Aids carbohydrate metabolism
• Inositol (d-chiroinositol)
– Decreases insulin resistance
• Lentils, chickpeas, and broccoli all decrease insulin levels.
– Smith, P., What You Must Know About Vitamins, Minerals, Herbs, and
More. Garden City Park, NY: Square One Publishing, 2008.
90
Herbal Therapies
• Trigonella foerum-graecum (fenugreek)
– Interferes with absorption and digestion of sugars
• Uemura, T., “Diosgenin present in fenugreek improves glucose
metabolism by promoting adipocyte differentiation and inhibiting
inflammation in adipose tissue,” Mol Nutr Food Res m2010;
54(11):1596-1608.
91
Herbal Therapies (Cont.)
• Gymnema sylvestre
– Improves insulin sensitivity and interferes with the
absorption of glucose
– Also reduces total cholesterol, triglycerides, and LDL. May
increase HDL.
• Luo, H., et al., “Decreased bodyweight without rebound and
regulated lipoprotein metabolism by gymnemate in genetic
multifactor syndrome animal,” Mol Cell Biochem 2007;
299(1-2):93-8.
92
Herbal Therapies (Cont.)
• Cinnamon
– Improves glucose utilization and increases insulin
receptor sensitivity
• FOS
• Cimicifuga racemosa (black cohosh)
– Binds to estrogen receptors and lowers LH
• Vitex agnus castus (chasteberries)
– Reduces prolactin secretion and lowers the estrogenprogesterone ratio
93
Herbal Remedies (Cont.)
• Serenoa repens (saw palmetto)
– Inhibits 5-alpha reductase so inhibits conversion of testosterone
to DHT
– Reduces androgen effects at the hair follicle and pilosebaceous
unit which decreases hirsutism and acne.
– 200 mg BID
• Ibid., Marchese.
• Pais, P., Potency of a novel saw palmetto ethanol extract, SPET-O85,
for inhibition of 5alpha-reductase II,” Adv Ther 2010; 27(8):555-63.
94
Herbal Therapies (Cont.)
• Urtica dioica (nettle)
– Nettle root binds to and increases SHBG decreasing the amount
of testosterone available for the body to use.
– 300 mg BID
• Nettle leaf does not work
– Chrubasik, J., et al., “A comprehensive review on the stinging nettle
effect and efficacy profiles. Part II: urticae radix,” Phytomedicine
2007; 14(7-8):568-79.
– Anon. “Urtica dioica; Urtica urens (nettle),” Monograph Altern Med
Rev 2007; 12(3):280.
– Ibid., Marchese.
95
Herbal Therapies (Cont.)
• Camellia sinensis (green tea)
– Increases SHBG which decreases testosterone
– Promotes weight loss
• Nagata, C., et al., “Association of coffee, green tea, and caffeine intakes
with serum concentrations of estradiol and sex hormone-binding globulin
in premenopausal Japanese women,” Nutr Cancer 1998; 30(1):21-4.
96
Herbal Therapies (Cont.)
• Camellia sinensis (green tea) (cont.)
– Placebo-controlled trial of women with PCOS showed that the
body weight of the group that used green-tea decreased by 2.4%.
– The weight and BMI of the control group was higher at the end of
the study.
– 270 mg of EGCG was used
• Chan, C., et al., “Polycystic ovary syndrome—a randomized placebocontrolled trial. Effects of Chinese green tea on weight and hormonal
and biochemical profiles in obese patients with PCOS,” Jour Soc
Gynecol Investig 2006; 13(1):63-8.
97
Herbal Therapies (Cont.)
• Glycyrrhiza glabra (licorice root)
– Can decrease testosterone synthesis
– Study using 3.5 grams of licorice containing 7.6% glycyrrhizic acid (0.25
grams total glycyrrhizic acid qd) for 2 months showed a reduction in
testosterone levels.
• Ibid., Marchese.
• Amanini, D., et al., “History of the endocrine effects of licorice,” Exp Clin
Endo Diabetes 2002; 110(6):257-61.
• Amanini, D., et al., “Licorice reduces serum testosterone in healthy
women,” Steroids 2005; 69:763-66.
98
Herbal Therapies (Cont.)
• Spearmint tea
– Lowers testosterone levels
– May raise FSH and LH
– May improve hirsutism
• Grant, P., t al., “Spearmint herbal tea has significant anti-androgen effects
in polycystic ovarian syndrome. A randomized controlled trial,” Phytother
Res 2010; 24:186-88.
99
Herbal Therapies (Cont.)
• D-chiro-inositol
– Placebo-controlled trial with 44 women. Half received D-chiro-inositol
1200 mg qd for 6-8 weeks.
– Insulin and testosterone levels were lowered in all of the women and
18 of them ovulated.
• Nestler, J., et al., “Ovulatory and metabolic effects of d-chiro-inositol in
the polycystic ovary syndrome,” NEJM 1999; 340:1314-20.
• Ibid., Marchese.
100
Herbal Therapies (Cont.)
• Maitake mushroom extract (Grifola frondosa)
– Study compared patients with PCOS that were given maitake
mushroom extract versus clomiphene.
– After 3 cycles
• Rate of ovulation in maitake group was 76.9%
• Rate of ovulation in clomiphene group was 93.5%
– Proposed mechanism of action is that maitake mushroom enhanced
insulin sensitivity
» Chen, J., et al., “Maitake mushroom (Grifola frondosa) extract
induces ovulation in patients with polycystic ovary syndrome: a
possible monotherapy and a combination therapy after failure with
first-line clomiphene citrate,” Jour Altern Complement Med 2010;
16(12):1295-99.
» Ibid., Marchese.
101
Detoxification
• Test patient for toxic metals and chelate if needed.
• Detoxify patient from any other toxin.
102
Supplements to Avoid With PCOS
• High doses of niacin
– Can worsen insulin sensitivity
103
Reference Book For Patients
– The PCOS Protection Plan by Colette Harris and Theresa Cheung. Hay
House Inc. 2006. Available worldwide.
104
Case #1
• 20-year-old patient with the chief complaint that she does not
cycle on a regular basis.
• PH: unremarkable
• FH: unremarkable
• SH: is a college student
• Medications: none
• ROS: negative
• P/E: normal
108
What Do You Want To Do
With This Patient?
109
Conclusion
• Doing a 28-day salivary test is very important to help evaluate
patients that may have PMS or PCOS.
110
Tests Referenced
•
•
•
•
•
•
Rhythm/ Rhythm Plus
Adrenocortex Stress Profile
Hormonal Health
PreD/ MetSyn
CV Health
Comprehensive Urine Elements Profile/ Toxic Element
Clearance
Q & A Session
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Balancing Younger Women’s Hormones
PMS, PCOS and Infertility
Pamela W. Smith, M.D., MPH, MS
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