ChiroCredit.com/OnlineCE.com Presents: Intro To Hormones 102

Salivary Hormone TestingPart 2

Women & Men’s Healthby

Ronald Steriti, ND, PhD© 2008

Salivary Hormones

The following hormones are typically in saliva:• All three Estrogens: Estrone (E1), Estradiol (E2),

and Estriol (E3)• Progesterone and Pregnenolone• Testosterone and Dihydrotestosterone (DHT)• Cortisol, DHEA and DHEA-S• Melatonin

Associated Diseases

• There are many diseases that are associated with hormonal imbalances

• Most (but not all) are womens and menshealth issues

• We will briefly describe each disease and the hormonal imbalance associated with it.

Hormonal Imbalance

• From a clinical standpoint, it is important to know when to suspect hormonal imbalance.

• The following list of diseases was compiled using conventional medical textbooks by searching for those with hormone imbalances in their etiologies.

Etiologies

• Most diseases have multiple etiologies. • Hormone imbalance is usually not the only

cause, and may not be the primary cause. • Hormonal imbalance may be causative or

secondary to other etiologies.• This is the art of medicine.

Premenopausal

• The premenopausal decline in androgens potentially is the most common cause of female androgen insufficiency (FAI), whereas natural menopause in itself is not a cause of androgen deficiency.

• Davis, SR (2002), ‘When to suspect androgen deficiency other than at menopause.’, Fertil Steril, 77 Suppl 4 S68-71. PubMed: 12007906

Menopause

• The traditional view of menopause is that it is caused by decreased production of estrogen by the ovaries

• The average age of menopause is 51, and virtually all women will be postmenopausal by age 58.

• Menopause is also associated with osteoporosis (which can cause fractures), and arteriosclerosis -coronary artery disease.

Psychologic Symptoms

• Psychologic symptoms (depression, nervousness, insomnia) are common with menopause

• Some believe that vasomotor symptoms are associated with hormonal imbalance, while psychological symptoms are not

• Psychological symptoms may be related to imbalances in tryptophan and serotonin

Menopause HRT

• In women with a uterus, it is recommended that physicians prescribe combination therapy only to treat menopausal symptoms such as vasomotor symptoms (hot flashes) and vaginal atrophy, using the smallest effective dosage for the shortest possible duration.

• Hill, DA, M Crider, and SR Hill (2016), ‘Hormone Therapy and Other Treatments for Symptoms of Menopause.’, Am Fam Physician, 94 (11), 884-89. PubMed: 27929271

Vasomotor Symptoms

• Vasomotor symptoms, including hot flashes and night sweats, are common during perimenopause.

• Night sweats are hot flashes with drenching perspiration that occur during the night, often disrupting sleep.

• In most women, hot flashes will abate over time without any intervention.

Thermoregulatory Dysfunction

• Estrogens are thought to modulate serotonin and norepinephrine, neurotransmitters that may play a role in thermoregulation.

• As estrogen levels fluctuate and decrease, serotonin and norepinephrine become imbalanced, resulting in thermoregulatory dysfunction that may lead to hot flashes and night sweats.

• Freedman, RR (2014), ‘Menopausal hot flashes: mechanisms, endocrinology, treatment.’, J Steroid Biochem Mol Biol, 142 115-20. PubMed: 24012626

Hot Flashes Treatments

• Hormones (estrogen and/or progesterone, or tibolone alone) are the most effective option available, resulting in an 80 to 90% reduction in hot flashes.

• The best non-hormonal treatment is newer SSRI antidepressants; for example, venlafaxine provides about a 60% reduction in hot flashes.

• Barton, D, C Loprinzi, and D Wahner-Roedler (2001), ‘Hot flashes: aetiology and management.’, Drugs Aging, 18 (8), 597-606. PubMed: 11587246

Estrogen and Hot Flashes

• Estrogen ameliorates hot flashes by increasing the core body temperature sweating threshold, although the underlying mechanism is not known.

• Sturdee, DW (2008), ‘The menopausal hot flush--anything new’, Maturitas, 60 (1), 42-49. PubMed: 18384981

Progesterone and VMS

• Progesterone effectively treats hot flushes and night sweats (vasomotor symptoms, VMS), improves sleep and may be the only therapy that symptomatic women, who are menopausal at a normal age and without osteoporosis, need.

• Prior, JC (2018), ‘Progesterone for treatment of symptomatic menopausal women.’, Climacteric, 21 (4), 358-65. PubMed: 29962247

Estrogen & Progesterone

• Some believe there is a balance between estrogen and progesterone

• Estrogen is “opposed” by progesterone in women (and testosterone in men)

• Therefore, decreased estrogen can result in symptoms of increased progesterone

• Steiner, M, E Dunn, and L Born (2003), ‘Hormones and mood: from menarche to menopause and beyond.’, J Affect Disord, 74 (1), 67-83. PubMed: 12646300

Hormone Replacement Therapy

• Many physicians are taking women off of hormone replacement therapy due to recent negative studies.

• This is usually difficult for patients that experience symptoms of menopause

Feedback Control

• Hormone production is controlled by a fairly complex feedback mechanism.

• Unfortunately, production is easy to turn off (with exogenous hormones), but not so easy to turn back on after several years.

Bioidentical HRT

• Bioidentical HRT uses the natural forms of hormones, instead of drugs

• It is considered a safer alternative to drugs• Salivary hormone testing is often used with

natural hormone replacement therapy to monitor and adjust the mix and dose.

• Holtorf, K (2009), ‘The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy’, Postgrad Med, 121 (1), 73-85. PubMed: 19179815

Osteoporosis

• Primary type I osteoporosis is caused by estrogen deficiency in postmenopausal women or athletes

• Although calcium and vitamin D receive all the press, bone building and resorption are controlled by estrogen and progesterone.

• Both estrogen (primarily estradiol) and progesterone effect osteoclast and osteoblast activity

• Prior, JC (2018), ‘Progesterone for the prevention and treatment of osteoporosis in women.’, Climacteric, 21 (4), 366-74. PubMed: 29962257

Pyrilinks-D • Although not a hormone, many salivary lab companies

offer the Pyrilinks-D test, which is useful as an indicator of bone resorption.

• About 90% bone is type I collagen, crosslinked by pyridinium, pyridinoline and deoxypyridinoline.

• Deoxypyridinoline is released during bone resorption and excreted in urine.

• Urinary Pyrilinks-D provides a quantitative measure of the excretion of deoxypyridinoline crosslinks as an indicator of bone resorption.

Premenstrual Syndrome

• PMS Type A is associated with high estrogen and low progesterone. The women become irritable and moody.

• PMS Type D is associated with low estrogen, high progesterone, and elevated androgens. Depression may be caused by low serotonin.

• PMS Type H is associated with elevated androgens (mostly testosterone). There is bloating and breast tenderness.

PMS

• The hormonal imbalances in PMS encompass estrogen, progesterone, testosterone and serotonin.

• It’s important to realize that the PMS types are diagnosed by symptoms, not by their hormone imbalances.

Premenstrual Dysphoric Disorder

• PMDD is much more severe than PMS • Irritability is a characteristic symptom.• Serotoninergic antidepressants such as

fluoxetine, citalopram, sertraline, and clomipramine are effective when used intermittently during the luteal phase of the menstrual cycle.

• Bhatia, S. C. and S. K. Bhatia (2002), ‘Diagnosis and treatment of premenstrual dysphoric disorder’, Am Fam Physician, 66 (7), 1239-48. PubMed: 12387436

PMDD Treatments

• Serotonin reuptake inhibitors are considered the first-line treatment.

• Second-line treatments include oral contraceptives containing drospirenone, other ovulation suppression methods, calcium, chasteberry, and cognitive-behavioral therapy.

• Lanza di Scalea, T and T Pearlstein (2019), ‘Premenstrual Dysphoric Disorder.’, Med Clin North Am, 103 (4), 613-28. PubMed: 31078196

Polycystic Ovary Syndrome

Symptoms of PCOS (Stein-Levanthol Syndrome) include:

• amenorrhea, oligomenorrhea, dysfunctional uterine bleeding, infertility, obesity, hirsutism, acne, acanthosis nigrans, hypertension, virilism, deep voice, enlarged clitoris and ovaries

PCOS Labs

• Labs show increased testosterone, DHEA, progesterone, estrone, androstenedione; and decreased sex hormone binding globulin (SHBG)

• Increased testosterone is the key diagnostic indicator

PCOS Etiology

• PCOS is associated with androgen excess, especially testosterone

• PCOS may be caused by a disruption of the hypothalamus-pituitary-ovarian (HPO) axis

Fibrocystic Breast Disease

• Breast lumps are common in young women and vary with the phase of the menstrual cycle

• The exact cause is unknown. • Possibilities include a luteal phase defect in progesterone,

increased estrogen, hypersensitivity to estrogen, sensitivity to methylxanthines (caffeine and chocolate), and dietary fat intake.

• Santen, RJ and R Mansel (2005), ‘Benign breast disorders.’, N Engl J Med, 353 (3), 275-85. PubMed: 16034013• Norwood, SL (1990), ‘Fibrocystic breast disease. An update and review.’, J Obstet Gynecol Neonatal Nurs, 19 (2),

116-21. PubMed: 2181087

Estradiol / Progesterone

A recent study found that even the slightest disturbance of the E2/P ratio may contribute to the occurrence of FBD with clinical manifestations of mastalgia and mastodynia.

Brkić, M, et al. (2018), ‘The Role Of E2/P Ratio In The Etiology Of Fibrocystic Breast Disease, Mastalgia And Mastodynia.’, Acta Clin Croat, 57 (4), 756-61. PubMed: 31168213

Fibroadenoma

• A fibroadenoma is a benign breast tumor that feels encapsulated, moves freely, has a rubbery consistency, and is circumscribed.

• They are more common young people• Fibroadenomas are estrogen dependent,

with rapid growth during pregnancy.• Ajmal, M and K Van Fossen (2019), ‘Breast Fibroadenoma’, StatPearls PubMed: 30570966

Uterine Fibroids

• Uterine fibroids are discrete, round, firm, benign uterine tumors made of smooth muscle and connective tissue

• They are the most common neoplasm, occurring in 25% of women over 35 years old

• They are stimulated by estrogen during reproductive years, and often grow during pregnancy

• De La Cruz, MS and EM Buchanan (2017), ‘Uterine Fibroids: Diagnosis and Treatment.’, Am Fam Physician, 95 (2), 100-7. PubMed: 28084714

Endometriosis

• Endometriosis is ectopic uterine mucosa (endometrium) found in various locations

• It responds to estrogen and progesterone (birth control pills and progesterone are used to treat it) and usually ends after menopause.

• Pregnancy may relieve the condition.• Schrager, S, J Falleroni, and J Edgoose (2013), ‘Evaluation and treatment of endometriosis.’, Am Fam Physician, 87

(2), 107-13. PubMed: 23317074

Endometrial Hyperplasia

• The primary presenting symptom of endometrial neoplasia is abnormal uterine bleeding. An endometrial biopsy rules out carcinoma.

• 70% are benign, 15% are diagnosed with carcinoma and 15% receive a diagnosis of endometrial hyperplasia

• Lacey, JV and VM Chia (2009), ‘Endometrial hyperplasia and the risk of progression to carcinoma.’, Maturitas, 63 (1), 39-44. PubMed: 19285814

• Wouk, N and M Helton (2019), ‘Abnormal Uterine Bleeding in Premenopausal Women.’, Am Fam Physician, 99 (7), 435-43. PubMed: 30932448

EH and Hormones

• EH is usually caused by continuous exposure of estrogen unopposed by progesterone, PCOS, tamoxifen, or hormone replacement therapy.

• Cyclic progestin or hysterectomy constitutes the major treatment options

• Chandra, V, et al. (2016), ‘Therapeutic options for management of endometrial hyperplasia.’, J Gynecol Oncol, 27 (1), e8. PubMed: 26463434

Dysfunctional Uterine Bleeding

• DUB is abnormal uterine bleeding (heavy or spotting) usually associated with anovulation

• It is caused by unopposed estrogen, tumors producing estrogen, exogenous estrogen, polycystic ovary syndrome, anticoagulants, and hormonal imbalance

DUB Treatments

• NSAIDs are the agents of choice for menorrhagia, although oral contraceptives, danazol and newer hormonal agents may also be used

• Bongers, MY, BW Mol, and HA Brölmann (2004), ‘Current treatment of dysfunctional uterine bleeding.’, Maturitas, 47 (3), 159-74. PubMed: 15036486

• Farrell, E (2004), ‘Dysfunctional uterine bleeding.’, Aust Fam Physician, 33 (11), 906-8. PubMed: 15584330• Rosenfeld, JA (1996), ‘Treatment of menorrhagia due to dysfunctional uterine bleeding.’, Am Fam Physician, 53 (1),

165-72. PubMed: 8546043

Secondary Amenorrhea

• Cessation of menses for 6 consecutive months in a woman past menarche who is not pregnant

• Amenorrhea has an extensive list of causes, many of which are hormonal (estrogen and progesterone imbalances).

• These include menopause, POS, premature ovarian failure, hysterectomy, and endocrine disorders

Migraines

• Migraines may be precipitated by the menstrual cycle and oral contraceptives

• They are also more common in women• Some studies show that migraines are

associated with estrogen deficiency• Hauser, L (2012), ‘Migraines and perimenopause: helping women in midlife manage and treat migraine.’, Nurs

Womens Health, 16 (3), 247-50. PubMed: 22697229• Chavanu, KJ and DC O’Donnell (2002), ‘Hormonal interventions for menstrual migraines.’, Pharmacotherapy, 22

(11), 1442-57. PubMed: 12432971

Acne vulgaris

• Androgens stimulate the rate of keratin turnover in sebaceous glands

• Androgenic steroid abuse and some birth control pills can cause acne

• Testosterone and DHT are sometimes measured

Androgenic Alopecia

• Androgenic alopecia is hair loss in either sex caused by stimulation of the hair roots by male hormones (testosterone and DHT).

• It can be caused by adrenal hyperplasia, POS, ovarian or pituitary hyperplasia, carcinoid

• Drug causes include: testosterone, danazole, ACTH, anabolic steroids, progesterone

Gynecomastia

• A benign glandular enlargement of the male breast that is generally bilateral

• It can be caused by exposure to high levels of estrogen compared to tesosterone

Benign Prostatic Hyperplasia

• Benign prostatic hypertrophy is a growth of prostate that may result in bladder outlet obstruction.

• BPH is seen in older men: – 50% of men over the age of 50; and – 80% of men over the age of 70. McNicholas, T and R Kirby (2012), ‘Benign prostatic hyperplasia and male lower urinary tract symptoms.’, Am

Fam Physician, 86 (4), 359-60. PubMed: 22963025Edwards, JL (2008), ‘Diagnosis and management of benign prostatic hyperplasia.’, Am Fam Physician, 77 (10),

1403-10. PubMed: 18533373

Etiology

• The exact etiology is unknown• Evidence suggests BPH arises from a systemic

hormonal alteration that may or may not act in combination with growth factors stimulating stromal or glandular hyperplasia

• Conventional treatment is with 5-alpha reductaseinhibitors (5-ARIs) finasteride and dutasteride

Labs

• Assessments of testosterone and dihydro-testosterone are recommended.

• Some studies measure the diurnal variation of testosterone using 4 samples in a 24-hour period.

• Measurement of DHT is based on inhibiting 5-alpha reductase, which converts testosterone into DHT.

Male Menopause

• Male menopause (andropause) involves the hormonal, physiological and chemical changes that occur in all men generally between the ages of 40 and 55.

• Approximately 40% of men in their 40-60s will experience some degree of lethargy, depression, increased irritability, mood swings, and difficulty in attaining and sustaining erections that characterize male menopause.

• Stolberg, M (2007), ‘From the “climacteric disease” to the “male climacteric” The historical origins of a modern concept.’, Maturitas, 58 (2), 111-16. PubMed: 17716839

Testosterone

• Many endocrinologists and scientists who have pioneered hormone studies say the phenomenon of male menopause correlates with a decline in testosterone levels.

• Testosterone is the hormone that stimulates sexual development in the male infant, bone and muscle growth in man and is responsible for sexual drive.

Low Testosterone

• Low testosterone has been found to cause fatigue, depression, loss of concentration, as well as decreased muscle strength and endurance.

• Testosterone is more important in libido or sex drive than in the erectile mechanism.

• Men with low testosterone levels usually have problems with erections.

• Channer, KS and TH Jones (2003), ‘Cardiovascular effects of testosterone: implications of the “male menopause”’, Heart, 89 (2), 121-22. PubMed: 12527649