The Steroidogenic Pathways


Hormones do not exist or function in isolation and we would be remiss if we did not incorporate the precursors to estrogen, progesterone and testosterone. (1)


All sex hormones, male and female originate with Cholesterol.  When total cholesterol is consistently below 140, we begin to see a disruption in the sex hormones.

Cholesterol begets Pregnenolone which, in turn, becomes DHEA, estrogen, progesterone, testosterone and cortisol.

Pregnenolone blocks the effects of cortisol, increasing resistance to stress and reducing pain and inflammation.  It enhances energy and improves nerve transmission and memory.

Pregnenolone helps to repair nerve damage, improves mood, sleep, learning, memory, and alertness.

Pregnenolone deficiency results in arthritis, insomnia, poor focus, memory loss, fatigue, depression and an inability to handle stress.

Pregnenolone depletes with aging.  By age 75 Pregnenolone, on average, is 65% lower than at age 35.  Excess saturated or trans-fats, hypothyroidism, certain tumors and too low cholesterol all contribute to Pregnenolone depletion.

Pregnenoloneoverload results in drowsiness, fluid retention, headaches, palpitations, irritability, and insomnia.

Optimal blood levels of Pregnenolone for men is 180 ng/dl and 200 ng/dl for women. (2) 

DHEA, is produced in the adrenal glands, brain and skin.  Like the other hormones, it declines with age.  By age 70 we only make 10-20% the amount present at age 20.

DHEA, known as the “mother of the body’s” steroids, produces estrogen and testosterone in both women and men.

DHEA increases ones’ sense of wellbeing, improves immune function, aids in repair of tissue, alleviates allergic reactions, increases brain function, lean body mass, lowers triglycerides, and helps prevent blood clots.  It plays a role in improving insulin sensitivity and preventing adult onset diabetes. (3)

DHEA reduces cardiovascular risk by increasing lipolysis, decreasing cholesterol and body fat.  DHEA acts as an antioxidant and slows the aging process in animals.

DHEA acts as an antidepressant, prevents, insomnia, osteoporosis, atherosclerosis, and reduces the need for insulin.

DHEA deficiency is due to menopause, stress, aging and tobacco use.

DHEA excess can result in fatigue, anger, insomnia, weight gain, mood changes, facial hair, acne, irritability, poor sleep and sugar cravings.

Optimal DHEA serum blood levels for men is 500-600 mg/dl.

Optimal DHEA serum blood levels for women is 200-250mg/dl.

Side effects include acne and hirsutism.


Dihydrotestosterone (DHT) normally is 10-15% of total testosterone.

DHT has positive effects on libido and energy.

DHT accelerates hair loss, enlarges the prostate, causes acne reduces sperm production, can result in erythrocytosis, gynecomastia, fetal virilization and sleep apnea.

Optimal blood levels are 100-500 ng/dl

Treatment: (1) Finasteride 1 mg/d, (2) Dutasteride 0.5 mg/d. (3) Saw Palmeto (not effective for hair loss.

Cortisol, produced in the adrenal gland, is one of two hormones that increase with age.  (Insulin is the other.)

Cortisol  is produced as a response to stress.  When agitated, the adrenals pump out large amounts cortisol.  If the body is able to handle the stress, it metabolizes the cortisol decreasing the level back to “normal.”

When one is “overstressed ”(and who isn’t?), cortisol remains high in the circulation resulting in irritability, sugar cravings, immune deficiency, chronic fatigue, weakness between meals, night sweats, high blood pressure, elevated lipid levels, elevated blood sugar, infections, thin skin, easy bruising, abdominal fat, insomnia and impaired thyroid function.

Cortisol balances blood sugar, controls weight, bone turnover, the immune response, sleep, protein synthesis, thoughts and mood.

Abnormal cortisol levels are seen with menopause, chronic fatigue syndrome, fibromyalgia, depression, impotence, diabetes, heart disease, infertility, insomnia and rheumatoid arthritis.

When cortisol increases, it decreases the progesterone production.

When cortisol is elevated, thyroid hormone is more bound and less active.

The preferred laboratory test for Adrenal Fatigue is a four point saliva test.  Saliva is tested at four different times in one day along with salivary DHEA-S, Progesterone, Estrogens, and Testosterone.  A blood sugar (can use hand held meter) along with the cortisol levels is useful.

Treatment of elevated cortisol (Adrenal Fatigue) is accomplished by replacing DHEA, adding adaptogenic herbs, licorice (not movie licorice, the herb), a proper anti-inflammatory diet, and a variety of nutrients including a multi-glandular designed to support adrenal function, Vitamins B and C, calcium, magnesium, zinc, selenium,, copper, manganese, phosphatidylserine, fish oil, cortef, and stress reduction techniques.

Insulin converts blood sugar into triglycerides, keeps blood sugar from elevating, increases muscle development and counters the effects of adrenaline and cortisol in the body.

Testosterone lowers blood sugar in males.  (Estrogen lowers blood sugar in women.)

Insulin deficiency results in bone loss, depression, fatigue and insomnia.  Too much insulin causes acne, asthma, breast and colon cancer, mood swings, heart disease, diminished testosterone levels, heart disease, GERD, high blood pressure, high cholesterol, and insomnia.

Insulin Deficiency results from a no to low carbohydrate diet, malnutrition and over exercising.

Insulin levels rise after a meal to reduce blood sugar, then level out after several hours.  If the system is constantly bombarded with substances attended by insulin, the insulin levels will not level off leading to production of inflammatory chemicals and cortisol.  Serum insulin will rise years before fasting glucose abnormalities are detected in the blood.

Insulin excess results from a high carbohydrate diet, sugared drinks, low fat diets, excess caffeine or saturated fat intake, hyperthyroidism, low estrogen levels, high testosterone levels, lack of exercise, smoking, beta blockers, steroids, diuretics and antidepressants.

Nutritional factors that can improve insulin levels include an anti-inflammatory diet, adding soluble fiber (oat bran), omega 3 fatty acids, chromium, alpha lipoic acid, vanadium, an antioxidant multivitamin (Vitamins A,C, E, and activated selenium at a minimum), coenzyme q 10, cinnamon, green coffee extracts, green tea and maitake mushrooms.

Optimal serum insulin levels are 5-10 microunits/ml.

Optimal glucose to insulin ration is 10/1.

Melatonin is generatedmainly in the pineal gland and secondarily in the retina, GI tract, and white blood cells, and plays a major role in the body’s daily circadian rhythm.  It helps regulate sleep patterns and is useful for insomniacs and jet lag.

Melatonin is made from tryptophan.  It needs B vitamins to be converted into a useful form.  Melatonin acts as an antioxidant, decreases cortisol, supports immune function and blocks estrogen from binding to receptor sites.

Melatonin is a potent anti-oxidant, protecting against cancer.

Melatonin has been touted as an estrogen–free form of birth control(9) and experiments suggest it has life lengthening properties.(10)  Melatonin improves mood, sleep quality, stimulates production of growth hormone and the parathyroid gland and balances the stress response.

Melatonin lowers blood pressure, decreases frequency of migraines and cluster headaches, reduces nocturiaands improves one’s quality of life.

Melatonindeficiency’s are noted with alcohol, caffeine and tobacco excesses, certain medications and close proximity to electromagnetic fields.

Melatonin excess can occur with intake of  bananas, cherries, ginger, oats, rice, corn, tomatoes walnuts, certain medications, St. John’s Wort and over exercise.

Melatonin is best administered in the compounded micronized form.

Dose is 3-30 mg titrated to effect one hour before sleep.

10% of patients have no reaction to melatonin.  1 % have an adverse-stimulatory effect.  It is minimally effect for tose addicted to sleeping pills.

A (positive) Side effects include mild grogginess and a reversal of hair color toward the color of youth.

Growth Hormone declines75% from young adulthood through midlife.  The loss of growth hormone results in a decrease in lean body mass, expansion of adipose(fat) tissue and thinning of the skin.

Growth Hormone administration prevents cardiovascular disease, improves lung function, enhances sexual performance, and hair re-growth.

Growth hormone deficiency increases the risk of cardiovascular disease, with smaller hearts, lower cardiac output and higher serum lipid concentrations.

Growth hormone replacement results in reduction in triglycerides, total cholesterol, and LDL (“bad cholesterol”).

Thickening of the walls of the carotid arteries (which leads to strokes) are reduced, resulting in improved blood flow to the brain.

Growth hormone deficiency results in a two-fold increase in cancer as compared to normal levels, decreased vitality, energy, physical mobility, feelings of social isolation and diminished sexual function even with adequate sex hormone levels.

Basal metabolic rate can increase from 6-11% after 6 months of therapy.  Across the board quality of life markers including energy, mood, pain sensitivity, emotional ability and physical mobility improved with growth hormone administration.

Sleep disturbances in midlife and beyond reliably track the decline in

growth hormone.  Restoration of growth hormone to an optimal level restores slow wave and REM sleep. (11)

Bone mineral density is increased 6-15% with the greatest gains in women receiving estrogen and bisphosphonate (Fosamax, Actonel, etc.) therapies.

Positive Effects of Growth Hormone Replacement Are Not Evident for at Least 6 Months.

Side effects of growth hormone (dose-dependant) are edema, arthralgias and myalgias, specifically carpal tunnel syndrome, and short term glucose intolerance.

No long term changes in fasting blood sugar or insulin levels were noted in both seven year and ten year studies. There is a transient, 1-6 week increase in sinulin resistance.  This can persist up to 18 months but without any evidence of increased incidence of diabetes versus the general population. (12)

There is no evidence growth hormone replacement increases the risk of cancer.

Growth Hormone is monitored with IGF-1 levels.  Optimal IGF-1 levels for adults are 300-350 ng/ml.  Side effects are noted when the blood level exceeds 380 ng/ml.

Dose of growth hormone is 0.1 mg/d subcutaneously.  This may be increased to 0.2, 0.4, 0.8 to a maximum of 1.2 mg/day

  1. http://media-cache
  2. Tsujimura, A, et. al. “Treatment with human chorionic gonadotropin for PADAM.” Aging Male, 2005 Sept-Dec.; 8(3-4):175-179
  3. Hanaway, Patrick, Estrogen Metabolism Hormone Essentials: Presentation @A4M Lecture Series, Las Vegas, NV, December 10, 2010
  5. Hertoghe; The Hormone Handbook, 2006, International Medical Publications, UK, p. 221.
  6. Bassil, et al, “The benefits of testosterone replacement therapy, a review,”  Therpeutics and Clinical Risk Management 2009: 5 427-448.
  8. Tsujimura, A, et. al. “Treatment with human chorionic gonadotropin for PADAM.” Aging Male, 2005 Sept-Dec.; 8(3-4):175-179
  9. Hanaway, Patrick, Estrogen Metabolism Hormone Essentials: Presentation @A4M Lecture Series, Las Vegas, NV, December 10, 2010
  11. Hanaway, Patrick, Estrogen Metabolism Hormone Essentials: Presentation @A4M Lecture Series, Las Vegas, NV, December 10, 2010


Other Hormones Symptoms

Growth Hormone DHEA
__Thinning Hair __Dry Hair
__Sagging Cheeks __Dry Skin and Eyes
__Receding Gums __Flabby Muscles
__Flabby Abdomen __Flabby Abdomen
__Slack Muscles __Little Hair Under Arms
__Skin Thin and Dry __Scant Pubic Hair
__Poor Recovery from Physical Activity __Scant Fatty Tissue in Pubic Area
__Profound Fatigue __Noise Intolerance
__Isolates Self “I hate everyone” __Poor Libido
__Overwhelming Anxiety and Worry __Poor Sexual Scent
Melatonin Insulin
__Aging Faster Than Peers __Craves Sweets
__Difficulty Falling Asleep __Always Thirsty
__Difficulty Staying Asleep __Urinates Frequently
__Mind Races at Night __Slow Healer
__Difficulty Recovering From Long Trip __Skinny Stomach and Buttocks
__Night Shift or Swing Shift Worker  
__Lives Out of “Sync” W World  
__Often Jet Lagged  
__Often Takes Sleeping Pills  
__Tired On Rising  

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