At menopause, a woman’s ability to produce her own endogenous hormones is significantly reduced. Menopause can be ultimately recognized by the cessation of menses for at least one year and, although it is not a disease, the transition into menopause is often accompanied by inconvenient symptoms. While the whole etiology of these symptoms is not completely understood yet, they can affect women both physically and psychologically, and can vary in frequency, as well as intensity.
The most common symptoms include hot flashes, mood changes, depression, cognitive changes, vaginal dryness, decreased libido, dyspareunia, decreased energy, sleep disturbances, and weight gain.
Hot flashes are the hallmark symptom of estrogen fluctuation, which occurs during the menopausal transition. A hot flash is generally characterized by a sudden sensation of intense body heat, often accompanied with profuse sweating of the head, neck, and chest. In most cases, the hot flashes occur at night, lasting several seconds to minutes, and can result in significant sleep deprivation, however many women suffer from them during the daytime as well. Heart palpitations, anxiety, irritability, and panic may go along with hot flashes. Although not life threatening, hot flashes can significantly affect a woman’s quality of life, functional ability, sexuality, and self-image.
Physiology of Hot Flashes
The exact mechanism of the hot flashes remains unknown. One of the theories of hot flash physiology is that a reduction in endorphin production decreases the set point of the thermoregulatory center in the hypothalamus. A reduction in the thermoregulatory set point will lead to heat loss, resulting in a hot flash as the body attempts to maintain a temperature within the set point. It has been postulated that norepinephrine levels are directly correlated with this reduction in the thermoregulatory set point.
Studies have demonstrated an increase in norepinephrine levels in the brain both prior to and during a hot flash. Estrogen enhances the synthesis of serotonin and endorphins, and serotonin and endorphins are believed to inhibit the production of norepinephrine.
According to one hot flash model, estrogen withdrawal leads to decreased blood levels of endorphins and serotonin and an increase in serotonin receptors, resulting in a loss in the feedback inhibition of norepinephrine production and a reduction in the thermoregulatory set point. Thus, agents that increase estrogen, serotonin, and endorphin levels or that decrease central norepinephrine release would be expected to reduce hot flashes.
Tryptophan and 5-Hydroxytryptophan (5HTP): Serotonin Precursors
Tryptophan is the amino acid precursor of serotonin. The amount of tryptophan that can be shunted into serotonin production is dependent on many variables, including the amount of niacin present and the availability of the substrate. Only free plasma tryptophan can cross the blood brain barrier via a carrier protein to enter the central nervous system (CNS). Once in the CNS, tryptophan is converted to
5HTP and then is decarboxylated to serotonin. The levels, and possibly function, of several neurotransmitters can be influenced by the supply of their dietary precursors. A reduction in tryptophan has been correlated to a reduction in serotonin. Tryptophan increases serotonin synthesis in the brain and may stimulate serotonin release.
Why 5HTP may be helpful for Hot Flashes?
Given the current understanding of hot flash physiology, the mechanism is likely due to increased serotonin and endorphin production, thereby increasing the set point of the brain’s thermoregulator. Clinical trials of 5HTP for depression and related disorders show that the mechanism for improvements in symptoms may be due to an increase in serotonin levels. Theoretically, 5HTP supplementation would have the ability to increase the amount of serotonin available, thus producing a similar effect to the SSRIs without the potential drawbacks. To date there are no direct comparative studies available to support this theory.
A study published in 2005 in the “Alternative Medicine Review” found that the administration of 5-HTP reduced the hot flash symptoms in menopausal women. According to researchers, the mechanism for improvements in symptoms may also be due to an increase in serotonin levels in the brain.
However, another study of 2010, sponsored by National Institute of Aging, brought opposite outcomes. In a small study, 24 menopausal women were randomized to receive 5-HTP (150 mg once per day) or placebo. The researchers, using a special device to measure the women's hot flashes, found that the subjects who took 5-HTP experienced no reduction in the frequency of hot flashes compared to placebo.
Other Therapeutic Uses
The currently established primary use of 5-HTP is for clinical depression. Several small short-term studies have found that it may be as effective as standard antidepressant drugs. Since standard antidepressants are also used for insomnia and anxiety, 5-HTP has also been suggested as a treatment for those conditions, but there is only very preliminary evidence as of today, that it actually works.
Similarly, antidepressant drugs are often used for migraine headaches. Some, but not all, studies suggest that regular use of 5-HTP may help reduce the frequency and severity of migraines, as well as help other types of headaches. Additionally, preliminary evidence suggests that 5-HTP can reduce symptoms of fibromyalgia and perhaps help you lose weight.
No significant adverse effects have been reported in clinical trials of 5-HTP. Side effects appear to be generally limited to short-term, mild digestive distress and possible allergic reactions.
One potential safety issue with 5-HTP involves an interaction with a medication used for Parkinson's disease: carbidopa. Several reports suggest that the combination can create skin changes similar to those that occur in the disease scleroderma.
According to several reports, when dogs have consumed excessive amounts of 5-HTP, they developed signs of excess serotonin. In humans, this so-called serotonin syndrome includes such symptoms as confusion, agitation, rapid heart rate, high blood pressure, muscle jerks, loss of coordination, sweating, shivering, and fever; rapid breathing, coma, and death are possible. Serotonin syndrome might also occur if 5-HTP is combined with drugs that raise serotonin levels, such as SSRIs (such as, Prozac), other antidepressants, or the pain medication tramadol.
Source and Dosage
5-HTP is not found in foods to any appreciable extent. For use as a supplement, it is manufactured from the seeds of an African plant (Griffonia simplicifolia).
A typical dosage of 5-HTP is 100 to 300 mg 3 times daily. Once 5-HTP starts to work, it may be possible to reduce the dosage significantly and still maintain good results.
A study published in 2009 in “Maturitas” found that 5-HTP at a dosage of 150 mg daily had a mild effect on the frequency of menopausal hot flashes.
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