Pregnenolone and Melatonin: Part of The Hormonal Symphony

by Pamela W. Smith, MD, MPH

Director of the Fellowship in Anti-Aging, Regenerative, and Functional Medicine

Codirector of the Master’s Program in Medical Science with a concentration in Metabolic and Nutritional Medicine, University of South Florida College of Medicine

Pregnenolone is commonly called the “mother hormone” since it goes on to make estrogen, progesterone, testosterone, DHEA, and cortisol. Pregnenolone therefore plays a major role in the hormonal symphony in the body. Pregnenolone is made from cholesterol. Consequently, if the patient’s total cholesterol level is too low, it becomes difficult for the patient to make enough pregnenolone and all of the downstream hormones as well.

The following are functions pregnenolone performs in the body:

• blocks the production of acid-forming compounds

• enhances nerve transmission and memory

• helps to repair nerve damage

• improves energy both physically and mentally

• improves sleep

• helps the body deal with stress

• modulates the neurotransmitter GABA

• modulates NMDA receptors which regulate pain control, learning, memory, and alertness

• promotes mood elevation

• reduces pain and inflammation

• regulates the balance between excitation and inhibition in the nervous system

Pregnenolone levels decline with age. By age 75, most patients have 65% less pregnenolone than they did at age 35. However, a patient may have low pregnenolone levels at any age if she is constantly stressed. The body then will preferentially take pregnenolone and make cortisol to help handle the pressure. Also, one’s ability to manufacture pregnenolone can be blocked if he eats trans-fatty acids or too much saturated fat. Furthermore, patients with hypothyroidism may have low pregnenolone synthesis.

The following are symptoms of low pregnenolone:

• arthritis

• depression

• fatigue

• inability to deal with stress

• insomnia

• lack of focus

• memory decline

Pregnenolone can be prescribed for the treatment of arthritis, depression, memory loss, fatigue, and moodiness. Supplementation with pregnenolone furthermore has been shown to be beneficial in the treatment of autoimmune diseases such as lupus, ankylosing spondylitis, and rheumatoid arthritis. Furthermore, medical trials have revealed that pregnenolone improves delta-wave sleep. As one ages, the amount of delta-wave sleep that she gets declines. This lowers melatonin levels and growth hormone production, which can lead to premature aging. Pregnenolone can also have a positive effect on the texture of the skin. Studies have shown that pregnenolone used topically, after 90 days, has a beneficial effect on participants’ skin. It was more hydrated, had fewer wrinkles, and appeared fuller in a clinically controlled trial.

Like any hormone in the body, a patient can produce or take too much pregnenolone. The following are symptoms of excess pregnenolone:

• acne

• drowsiness

• fluid retention

• headache

• palpitations

• insomnia due to overstimulation

• irritability, anger, anxiety

• muscles aches

Furthermore, since pregnenolone goes on to make the other sex hormones, the patient should not take pregnenolone without a doctor’s direction. All of the hormones in the body play in concert; if one if altered, it affects the hormonal symphony. It is always best to measure levels of this hormone before suggesting that the patient use it. Pregnenolone can be given orally or transdermally as part of hormone replacement therapy in both men and women. It should not be used in patients who have a history of breast or prostate cancer.

Melatonin, a hormone made by the pineal gland, also plays a key role in the hormonal concert. It is also crafted in the retina, the gastrointestinal tract, and the white blood cells. Melatonin sets the circadian rhythm of the body by resetting its biological time clock. Melatonin causes drowsiness and lowers body temperature when it is time for sleep.

Melatonin is made from the amino acid tryptophan, which is also used to make serotonin. When melatonin levels go up, serotonin levels decline. If the patient eats too many high-sugar carbohydrates, he will make less melatonin, since carbohydrates shift the amino acid balance to make more serotonin. Furthermore, the body needs B vitamins in order to convert tryptophan into melatonin. Therefore, if the patient does not eat enough vitamin B-rich foods or does not take a supplement, she may become deficient in melatonin.

Melatonin serves more purposes than simply monitoring the body’s internal clock. It has the following influences in the body:

• affects the release of sex hormones

• aids the immune system in working normally in the body

• antioxidant activity (it is a more potent antioxidant than vitamins C or E)

• blocks estrogen from binding to estrogen receptors

• decreases cortisol levels (in previous articles, the importance of normal cortisol levels has been discussed)

• helps balance the stress response

• helps prevent cancer

• improves mood

• improves the quality of sleep

• increases the action of benzodiazepines

• stimulates the parathyroid gland

• stimulates the production of growth hormone

Medical trials have also shown that melatonin levels are lower in patients with heart disease. Since endogenous levels of melatonin in older patients are reduced, it predisposes them to more severe cardiac damage during a heart attack. Melatonin has been shown to reduce hypoxia and prevent reoxygenation-induced damage after cardiac ischemia and ischemic stroke. Furthermore, studies have also shown in laboratory animals that melatonin may be effective against ventricular fibrillation and other arrhythmias. Melatonin is a vasodilator and free radical scavenger, and it has been shown to inhibit oxidation of LDL-C. Likewise, melatonin protects cardiac myocyte mitochondria. In addition, in animal trials, melatonin supplementation suppressed male rat intra-abdominal visceral fat and returned plasma insulin to youthful levels.

The following are causes of melatonin deficiency:

• alcohol

• caffeine

• electromagnetic fields

• medications

  • acetaminophen

  • aprazolam

  • aspirin

  • atenolol

  • benserazide

  • bepridil

  • clonidine

  • dexamethasone

  • diazepam

  • diltiazem

  • filodipine

  • flunitrazepam

  • fluoxetine

  • ibuprofen

  • indomethacin

  • interleukin-2

  • isradipine

  • luzindole

  • methylcobalamin

  • metoprolol

  • nicardipine

  • nifedipine

  • nimodipine

  • nisoldipine

  • Nitrendipine

  • prazosin

  • propranolol

  • reserpine

  • ridazolol

• tobacco

As with all other hormones, elevated levels of melatonin can have side effects, such as daytime sleepiness and fatigue, depression, headaches, increase in cortisol, intense dreaming and/or nightmares, and suppression of serotonin. Melatonin levels can be measured in the body by doing a salivary test. As with all hormones, it is always best to measure levels to see if the patient needs melatonin and to aid in finding the appropriate dosage.

The following are reasons that the body may have too much melatonin:

• exercise

• foods

  • bananas

  • barley

  • cherries

  • cherries

  • ginger

  • oats

  • rice

  • sweet corn

  • tomatoes

  • walnuts

• medications

  • clorgyline

  • desipramine

  • fluvoxamine

  • thorazine

  • tranylcypromine

• St. John’s wort

• supplementing with melatonin

Melatonin is an immune stimulator; therefore, if the patient has an autoimmune disease, supplementation should be done with caution and only with the help of a health-care practitioner. If the patient is pregnant, breast-feeding, on prescription steroids, or has depression or other mental illness, lymphoma, or leukemia, melatonin should not be taken. Furthermore, if the patient has too high of levels of melatonin, then estrogen and testosterone levels may be suppressed. The symphony of the hormones in the body must play in tune in order for the patient to have optimal health.

This article is an excerpt from: P. Smith. What You Must Know About Woman’s Hormones. Garden City Park: Square One Publishers; 2010. References to this article are located in that text.