Download Hormone Health IG Premenopausal

ENDOCRINE ASSESSMENTS
Premenopause
Why is this test important?
This profile provides clinicians with a deeper, more precise understanding of sex steroid
metabolism, enabling them to better assess the impact of hormonal imbalances on each
woman’s health. It also helps target candidates for hormone replacement therapy (HRT)
and provides an easy means of monitoring bio-identical hormone therapy or other
interventions along the way..
This comprehensive profile includes measurements of the three major estrogens, two
estrogen metabolites that reflect breast cancer risk, two major androgens, progesterone,
and sex-hormone binding globulin.
What does this test involve?
All markers are measured in a single serum specimen. Three versions of the profile are
available: premenopausal (specimen collected at peak of luteal phase), menopause, and
menopause & HRT (specimen collected 8-10 hours after the last hormone dose). The test
report includes commentary and a map of the hormones showing their interrelationships.
Due to the diversity of forms and protocols for HRT, the ‘Menopause & HRT’ version of the
profile utilizes pre-menopausal follicular reference ranges.
What are the consequences of hormonal imbalances?
Sex steroids affect a wide array of functions in the body. Imbalances in many of the
hormones tested are associated with increased risk of gynecological disorders such as
menstrual irregularities, ovarian cysts and uterine fibroids, polycystic ovary syndrome,
infertility and spontaneous abortions, and sexual dysfunction. Risk may also be increased
for systemic problems such as osteoporosis, heart disease and dyslipidemia, immune
weakness, and breast cancer. Identifying clinically significant imbalances can help
clinicians to effectively customize treatment and optimize their patients’ health.
Additional support materials for this profile are available, including patient brochure
and One-Page Test Description. Refer to website www.gdx.net for more educational
documents.
INTERPRETIVE
GI U I D E L I N E S
NTERPRETIVE
GUIDELINES
Progesterone
Analyte
Progesterone
Result
Low
Suspect
• May indicate collection at time other than
luteal peak
• Luteal phase defect (impaired progesterone
production by corpus luteum)
• Anovulation*
• Chronic stress (steroid precursors shunted
toward cortisol production)
• Meds: Low progesterone common with oral
contraceptives (including recent discontinuation)
or ampicillin
Consider
• Address estrogen imbalances (see E2 and E1
sections of guide)
• Address underlying contributors to anovulation or luteal phase defect (see column to left)
• Anti-oxidants, especially carotenenoids, if
oxidative stress
• Support hypothalamic/pituitary/ovarian (HPO)
axis, e.g., chasteberry)
• Stress management, adrenal support
• Check FSH and LH to rule out early
menopause
• Glandular support for ovary, hypothalamus,
pituitary
• Address infection or inflammatory condition
• Progesterone or pregnenolone supplementation
High
• Adrenal hyperactivity
• Persistent corpus luteum
• Progesterone or pregnenolone supplementation
• Inhibitors of progesterone metabolism
(e.g., ketoconazole, cimetidine, cigarette smoke,
or glucocorticoids)
• May be seen in some cases of endometriosis,
depression-type PMS, or PCOS
• Stress management, adrenal support,
relaxant herbs, if relevant.
• Remove metabolic inhibitors
• Address any relevant underlying disorder
(see column to left)
Result
Low
Suspect
• Hypothyroidism
• Hyperinsulinemia
• High body mass index
• Western-type diet
• Low estradiol
• Alcohol intake
• Hyperprolactinemia
• Oral testosterone or high levels of endogenous
androgens
• Corticosteroids
• Meds: Danazol, glucocorticoids, insulin, Norplant,
norethindrone acetate (androgenic progestin)
Consider
• Attention to relevant underlying disorders
(e.g., normalize thyroid function, improve
insulin sensitivity, reduce body mass index)
• SHBG may be increased with isoflavones,
dietary fiber, flaxseed
High
• Hyperthyroidism
• Thyroxine therapy
• Significant weight loss
• Smoking
• Caffeine
• High fiber diet
• Oral estrogens or high levels of endogenous
estrogens
• Oral contraceptives
• Meds: tamoxifen, carbamazepine, clomiphene,
anti-convulsants, phenytoin, and rifampin
• Normalize thyroid function, if relevant
• DHEA supplementation may reduce SHBG,
at least in postmenopausal women
Binding Proteins
Analyte
Sex-Hormone Binding
Globulin (SHBG)
2
Androgens
Analyte
DHEA-S
(Dehydroepiandrosterone
sulfate)
Result
Low
Suspect:
• Chronic stress (adrenal fatigue or shunting of
precursors to cortisol production)
• Aging
• Hypocholesterolemia
• Inflammation (TNF activity)
• Smoking
• Meds: ketoconazole and anti-epileptics
Low DHEAS may be associated with depression,
high body mass index, impaired immunity,
dyslipidemia, reduced insulin sensitivity, reduced
bone mass, and chronic conditions such as
rheumatoid arthritis, lupus, chronic fatigue, and
cardiovascular disease
High
• Observed in PCOS (greater DHEA response
to ACTH)
• Insulin resistance with hirsutism
• Acute stress
• Adrenal hyperplasia or Cushing’s syndrome
• Hyperprolactinemia
• DHEA supplementation
• Meds: clomiphene
Consider:
• Stress management
• Adrenal support:
Nutrition (e.g., vitamin C, pantothenic acid, B6,
zinc, magnesium)
Herbal adrenal adaptogens (Siberian or Panax
ginseng, ashwaganda, etc. Avoid licorice
when cortisol is high)
Adrenal glandular
• Anti-inflammatory measures, if relevant
• DHEA supplementation
• Stress management, if relevant
• Address PCOS and/or hyperinsulinism
(e.g., weight reduction, exercise, reduce
carbohydrates and hydrogenated fats,
chromium, zinc, magnesium, alpha lipoic acid,
fish oils, meds such as metformin or pioglitizone)
High DHEAS may result in testosterone excess
in women
Analyte
Testosterone (total)
Result
Low
Suspect:
Ovarian or adrenal insufficiency (see DHEAS level)
• High aromatase activity (expect higher E2),
e.g., alcohol; glucocorticoids, inflammation,
glycerrhiza; hypothalamic or pituitary insufficiency
(also expect low estrogens, thyroid, and
adrenals); inflammatory conditions (TNF inhibits
production of its precursor, DHEA)
• Meds: ketoconazole, fluconazole, digoxin, danazol, glucocorticoids, nafarelin, spironolactone,
thioridazine, phenothiazines, troglitazone, oral
contraceptives, THC, or licorice (suppressed
production)
Consider:
• Support hypothalamic/pituitary/ovarian (HPO)
axis, e.g., chasteberry, adrenal adaptogen herbs
• Ovarian glandular
• Glandular supplementation (e.g., hypothalamus,
pituitary, adrenal)
• Address infection or inflammatory condition
(TNF reduced by fish oils, nettle leaf, green
tea, ginkgo biloba, N-acetyl cysteine, and
Eleuthrococcus, abdominal fat reduction)
• Rule out aromatase stimulation
• Consider aromatase inhibitors IF E2 and E1 are
high (e.g., chrysin, flavonoids, phytoestrogens,
flaxseed, procyanidins in grape seed and red
wine, progesterone (inhibits cortisol-induced
aromatase induction), non-steroidal aromatase
inhibitors, e.g., anastrozole (Arimidex)
• Testosterone or DHEA supplementation (also
reduces SHBG, thus increasing bioavailable
testosterone)
• Testosterone-enhancing herbs (e.g., Siberian
or Korean ginseng, ashwaganda, Tribulus
terrestris, horny goat weed)
High
• Ovarian (primarily) or adrenal hyperactivity
(refer to DHEAS)
• May be related to PCOS and/or insulin resistance
• Abdominal obesity
• DHEA supplementation
• Aromatase inhibition (e.g., smoking, chrysin,
flavonoids, ketoconazole, oxidative stress)
• Address PCOS and/or insulin resistance (e.g.,
weight reduction, exercise, reduce carbohydrates and hydrogenated fats, chromium, zinc,
magnesium, alpha lipoic acid, fish oils, medications such as metformin or pioglitizone)
Continued on next page
3
Analyte
Testosterone (total), cont’d
Result
High,
cont’d
Suspect
• Meds: barbiturates, cimetidine, clomiphene,
estrogens, rifampin, phenytoin
• Gonadotropin stimulation of ovary in perimenopause (may lead to spikes in testosterone)
• Associated with celiac disease in men
(low 5- reductase); not known if also applies to
women
Consider
• D-chiro-inositol (for PCOS)
• Oral contraceptives suppress ovarian (primarily)
Considerand adrenal androgen production
• Rule out testosterone-raising drugs or
aromatase inhibition
• Aromatase may be enhanced by boron,
vitamin D3, diindolylmethane (DIM), licorice
• Consider reducing dietary protein or fat,
increasing exercise
• Increase SHBG to reduce bioavailable
testosterone (e.g., isoflavones, dietary fiber,
flaxseed, oral estrogens)
Analyte
Free Androgen Index (FAI)
Result
Low
Suspect
Note: Refer to individual levels of SHBG and Total
Testosterone for most appropriate interpretation
Consider
Note: Refer to individual levels of SHBG
and Total Testosterone to determine most
appropriate target(s) for intervention
• Low total testosterone
• High SHBG
• Meds: antiepileptics, DES, digoxin, spironolactone,
phenothiazines, ketoconazole, THC,
SHBG-inducing meds
High
Note: Refer to individual levels of SHBG and Total
Testosterone for most appropriate interpretation
• High total testosterone
• Low SHBG
• Meds: barbiturates, clomiphene, danazol,
SHBG-reducing meds
Estrogens
Analyte
Estradiol (E2) and
Estrone (E1)
4
Result
Low
Suspect
(E2 most significant)
• Low body mass index (BMI)
• Strenuous exercise (may lead to anovulation
and less peripheral production of estrogen)
• Chronic stress (precursors shunted to production
of stress hormone or inhibitory HPA feedback
loops)
• Hypothalamic or pituitary insufficiency
• Chronic inflammation (see comment for low
DHEAS)
• Decreased conversion from androgens (check
for high testosterone) (e.g., smoking, chrysin,
flavonoids, ketoconazole)
• Meds: ketoconazole, oral contraceptives
(including recent use), cimetidine, megestrol
(anti-neoplastic agent)
Consider
• Support hypothalamic/pituitary/ovarian (HPO)
axis, e.g., chasteberry, adrenal adaptogen herbs
• Glandular supplementation (e.g., ovary,
hypothalamus, pituitary, adrenal)
• Stress management, adrenal support
(see comments for DHEAS)
• Increase BMI, if relevant
• If testosterone is elevated, rule out aromatase
inhibition (e.g., smoking, chrysin, flavonoids,
ketoconazole). Aromatase activity enhanced
with boron, vitamin D3 diindolylmethane (DIM),
licorice
• Broad-spectrum nutrition
• Common herbs with estrogen-like activity
include red clover, fennel, sage, hops,
black cohosh, licorice, panax ginseng,
fennel, anise
High
• Decreased hepatic clearance of estrogen
• High intestinal beta-glucuronidase activity
(increased reuptake of estrogen)
• High BMI
• Hypothyroidism
• Adrenal insufficiency (stimulatory HPA feedback
loops)
• Promote hepatic clearance (e.g., lipotropic
factors, liver botanicals, broad-spectrum
nutrition)
• Check stool for beta glucuronidase activity
• Reduce excess weight
Continued on next page
Analyte
Estradiol (E2) and
Estrone (E1), cont’d
Result
High,
cont’d
Suspect
• Smoking (higher E2 levels)
• Meds: clomiphene, tamoxifen, digoxin (for E1)
• Inflammation (cytokines increase conversion of
E1 to E2)
• Estrogen or androgen supplementation
High E2 may be associated with PMS
(esp. featuring anxiety or water retention;
progesterone may be low), breast tenderness,
irritability, dysmenorrhea, increased risk of
endometrial hyperplasia and CA (if not balanced
by progesterone), increased breast density and
breast CA risk, ovarian cysts, uterine fibroids,
and menometrorrhagia
Analyte
Estriol (E3)
Result
Low
Suspect
• Reduced conversion from 16 -hydroxyestrone
(check level)
• Meds: ampicillin, penicillin, aspirin, probenecid,
thyroxine, albuterol (although most effects seen
only in pregnancy)
Consider
• Increase exercise
• Increase dietary fiber (reduces enterohepatic
reuptake of estrogen)
• Stress management, adrenal support
• If testosterone is low, aromatase activity can
be reduced with chrysin, flavonoids,
phytoestrogens (esp. genestein), flaxseed
(enterolactone), procyanidins in grape seed
and red wine, progesterone (inhibits cortisolinduced aromatase induction)
• Stimulate SHBG, if low
(Note: will lower bioavailable testosterone)
• Phytoestrogens (e.g., soy isoflavones) act as
weak antagonists to estrogen when levels
are high
• Consider progesterone supplementation, to
balance (refer to progesterone value)
Consider
Note: Any intervention should be based on
levels of 16 -hydroxyestrone (refer to
‘Estrogen Metabolism’) and the other
estrogens
Low E3 results in higher net estrogen activity in
body (if E1 and/or E2 are higher)
High
• Generally results in lower net estrogen activity in
body (competitive antagonist to E1 and E2)
• Enhanced conversion from 16 -OHE1 (protective
effect on breast CA risk); OR associated with high
level of 16 -OHE1 (increased breast CA risk)—
Refer to level of 16 -OHE1
Estrogen Metabolism
Analyte
2:16 -Hydroxyestrone Ratio
Result
Low
Suspect
Low 2:16 -OHE1 ratio suggests shunting of estrogen metabolism to the more potent 16 -OHE1
and/or 4-OHE1 (check level of 16 -OHE1)
• Increased net estrogen activity in body
• Increased risk of breast cancer
• Rheumatoid arthritis
• Lupus (SLE)
• Greater bone mass, although possibly less likely
to show increases in BMD with HRT
Note: The above risks are modified when E1 and
E2 trend low
• Pesticide exposure
• Hypothyroidism
• Obesity
• High fat, low fiber diet
• Omega-6 fatty acids
• Alcohol consumption
• Meds: oral contraceptives
Consider
Note: Decision to modify ratio should be
based on patient’s respective risks for breast
cancer (high estrogen) and osteoporosis
(low estrogen)
To increase ratio:
• Cruciferous vegetables (e.g., broccoli,
cabbage, cauliflower)
• Indole 3-carbinol (I3C) or diindolylmethane (DIM)
• Flaxseed (lignans)
• Soy isoflavones (genestein, daidzein)
• Fish oils (omega-3 fatty acids)
• Reduce dietary fat
• Rosemary, kudzu, turmeric
Note: It is recommended for follow-up testing to
use same specimen type as used in this test
(blood versus urine)
Continued on next page
5
Analyte
2:16 -Hydroxyestrone Ratio,
cont’d
Result
High
Suspect
• High 2:16 -OHE1 ratio suggests shunting of estrogen metabolism away from the more potent 16 OHE1 and/or 4-OHE1 (check level of 16 -OHE1)
• Decreased net estrogen activity in body
• Decreased risk of breast cancer
• Studies on bone density are mixed: High ratio
(along with low estrogens) may correlate with
increased risk of osteoporosis. However, 2OHE1
stimulates osteoblasts, and women with higher
2:16 ratio appear to gain more bone with HRT.
Note: The above risks are modified when E1 and
E2 trend high
Consider
To reduce ratio:
• Apiaceous vegetables (e.g., carrots, parsnips,
celery, dill, parsley)
• Reduce intake of cruciferous vegetables,
soy, flax
Note: It is recommended for follow-up testing to
use same specimen type as used in this test
(blood versus urine)
• High intake of cruciferous vegetables, soy, flax
• High coffee consumption
• Regular alcohol consumption
• Smoking
• Meds: Prozac™, thyroxine
Add-on Markers
Analyte
Follicle Stimulating Hormone
(FSH) and
Luteinizing Hormone (LH)
Analyte
Androstenedione
6
Result
Low
Suspect
• Excess estrogen or testosterone (provides
negative feedback to anterior pituitary)
• Deficient progesterone (pre-menopausally)
• Glucocorticoid excess
• Excessive exercise
• Hyperprolactinemia (may suppress GnRH via
a dopamine-related mechanism)
• Hypothyroidism (TRH-induced prolactin
secretion)
• Possible PCOS (if low FSH along with high LH)
• Deficient hypothalamic secretion of GnRH
(including anorexia nervosa or genetic disorders)
• Pituitary insufficiency
• Congenital adrenal hyperplasia
• Radiation or trauma to pituitary
• Critical illness (transitory suppression)
• Prolonged administration of anabolic steroids
• Autoimmune damage to hypothalamus or pituitary
• Meds: Oral contraceptives, estrogens,
phenothiazines
Consider
• Identify and correct underlying cause
(see column to left)
• Refer to estrogen levels and suggested
interventions
• Refer to prolactin level and suggested
interventions
• Evaluate thyroid function
High
• Low estrogen or testosterone
• Primary ovarian insufficiency (premature ovarian
failure or onset of menopause)
• Hyperinsulinemia (increases LH); may cause
hyperandrogenism
• Congenital disorders (e.g., Turner Syndrome)
• Pituitary adenoma (FSH high, LH normal)
• Meds: L-dopa, clomiphene, ketoconazol
• Identify and correct underlying cause
(see column to left)
• Refer to estrogen level and suggested
intervention
• Rule out hyperinsulinemia (high LH)
Result
Low
Suspect
• Ovarian or adrenal insufficiency (see DHEAS
level)
• Hypothalamic or pituitary insufficiency (also
expect low estrogens, thyroid, and adrenals)
• High aromatase activity (expect higher estrone);
e.g., alcohol, glucocorticoids
Consider
• Identify and correct underlying cause
(see column to left)
Continued on next page
Analyte
Androstenedione, cont’d
Analyte
Prolactin
Result
Low,
cont’d
Suspect
• Inflammatory conditions (TNF inhibits
production of its precursor, DHEA)
• Hyperprolactinemia (stimulates adrenal
androgen production)
• Meds: carbamazepine, ketoconazole, Norplant™
High
• Ovarian or adrenal hyperactivity
(refer to DHEAS level)
• DHEA supplementation
• Aromatase inhibition (e.g., smoking, chrysin,
flavonoids, ketoconazole, oxidative stress)
• Licorice (inhibits conversion of androstenedione
to testosterone)
• Meds: clomiphene, metyrapone, cimetidine,
DHEA
Result
Low
Suspect
• Hyperthyroidism (prolactin inhibited by T3)
• Prolonged dopamine infusion
• Sheehan syndrome (post-partum pituitary
necrosis)
• Pituitary tumor, or treatment of tumor
• Head injury
• Infection (e.g., histoplasmosis, TB)
• Infiltrative diseases (e.g., hemochromatosis,
sarcoidosis)
• Bulimia
• Inborn error
• Meds: ergot derivatives, L-dopa, bromocriptine,
calcinonin, rifampin, valproic acid, tamoxifen
High
• Excess estrogen
• Pregnancy or post-partum
• Primary hypothyroidism
• Alcoholic cirrhosis
• Celiac disease (active)
• Hypoglycemia
• PCOS
• Insulin resistance
• Chest trauma or surgery
• Pituitary tumor (micro- or macroadenoma)
• Anti-prolactin antibodies (prolactin/IgG complex;
symptoms may be minimal)
• Intracranial tumors
• Meds: cimetidine, cocaine, estrogens, oral
contraceptives, haloperidol, methadone,
phenothiazines, tricyclic antidepressants, MAO
inhibitors, metoclopramide, reserpine, danazol,
phenytoin, verapamil, opiates
Consider
• Identify and correct underlying cause
(see column to left)
• Evaluate for PCOS (refer to levels of
testosterone, LH, and DHEA; if levels high,
check insulin
Consider
• Identify and correct underlying cause
(see column to left)
• Normalize thyroid, if high
• Remove prolactin-suppressing medications
• Identify and correct underlying cause
(see column to left)
• Pregnancy test, if relevant
• Refer to estrogen levels and suggested
interventions
• Normalize thyroid, if low
• Evaluate adrenal function
• Rule out celiac disease, remove gluten if
positive
• Improve insulin sensitivity
• Remove prolactin-inducing medications
• IgG Anti-prolactin antibodies
• MRI, if suspect tumor
• L-tyrosine? (dopamine inhibits prolactin)
• Vitamin B6
• Progesterone (inhibits prolactin in vitro)
• Dopamine agonists (e.g., bromocriptine,
pergolide, quinagolide)
• Ergoline derivatives (e.g., cabergoline)
• Surgery (large tumors causing visual field
deficit)
7
This information is for the sole use of a licensed health care practitioner and is for educational purposes only.
It is not meant for use as diagnostic information. All claims submitted to Medicare/Medicaid for Genova
Diagnostics laboratory services must be for tests that are medically necessary. “Medically necessary” is defined
as a test or procedure that is reasonable and necessary for the diagnosis or treatment of illness or injury or to
improve the functioning of a malformed body member. Consequently, tests performed for screening purposes
will not be reimbursed by the Medicare program.
63 Zillicoa Street
Asheville, NC 28801
800 522.4762
www.GDX.net
© 2008 Genova Diagnostics
e,ig,HormHealth_Pre,071408