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.
Recent Studies
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.
Safety Issues
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.
Sources and
Additional Information:
