Women in early menopause or perimenopause are most familiar with hot flashes: they’re generally understood to occur with declining estrogen levels. Occasionally I’ll see a still-menstruating woman who experiences hot flashes in the week or two before her period (when estrogen levels are declining), too—though this is much less common.
And yet, this isn’t the whole story. While there is a decided correlation between estrogen levels and hot flashes, and while estrogen replacement therapy (bioidentical or otherwise) is hands down the most effective treatment for them, lab values aren’t great at predicting who will struggle with hot flashes and who won’t. Some women with no measurable estrogen at all on lab work are just fine symptomatically, while others with apparently reasonable levels have a terrible time. So what is really going on—and how does that inform treatment options for those who can’t or choose not to use hormone replacement therapy?
Physiology 101: Temperature Regulation
The technical term for hot flashes is vasomotor symptoms, and the name is descriptive from a physiology standpoint: vaso- meaning involving blood vessels, and -motor meaning movement. Essentially, hot flashes are an abrupt version of the temperature regulation mechanisms your body has always used.
According to this study, our bodies should, and generally do, have a buffer range of acceptable temperatures, called the thermoneutral zone. This range is about 0.4 degrees Celsius. When the body climbs above the thermoneutral zone, it triggers a sympathetic nervous system (“fight or flight”) response: the release of norepinephrine or epinephrine activates sweating and peripheral vasodilation, meaning the blood vessels on the outside of the body dilate in order to release heat to the surrounding environment. Because there’s a buffer, this happens slowly in asymptomatic people, such that we don’t even notice it in most cases.
Women in peri- and early post-menopause, however, don’t appear to have a thermoneutral zone at all—or if they do, it is exceedingly small. This means that the least alteration in the core body temperature triggers a sudden and intense sympathetic response: peripheral vasodilation and sweating occur all at once, often followed by shivering when the body temperature dissipates too much heat.
So now the question becomes, why do dropping hormone levels trigger a collapse of the thermoneutral zone? And why doesn’t it happen every time the hormones are low—what other variables are involved that make up the difference?
How Hormones Affect Neurotransmitters
Estrogen and progesterone both affect a number of neurotransmitters, including serotonin, GABA, and perhaps most importantly, the catecholamines (dopamine, norepinephrine, and epinephrine.) Since we know norepinephrine and epinephrine are directly connected to the mechanism of action of hot flashes, let’s start with those.
Estrogen decreases the activity of the MAO enzyme, which breaks down catecholamines (including epinephrine). This means when you have adequate estrogen, you have more of the catecholamines to go around. Progesterone does the opposite: it increases MAO activity, which means you’re breaking catecholamines down faster. When they’re in balance, this means you have just enough of the catecholamines, but not too much: too much leads to anxiety, while too little leads to depression.
In menopause, estrogen and progesterone are both low, but generally estrogen is a little higher than progesterone, leading to estrogen dominance. Probably this is because progesterone is the precursor for cortisol, the stress hormone, and menopausal symptoms are stressful to the body. Estrogen dominance means more catecholamines, due to a relatively under-functioning MAO enzyme—and catecholamines are the neurotransmitters associated with vasomotor responses. This is one reason why sometimes just giving a menopausal woman progesterone, with no estrogen, can help hot flashes.
Very commonly, though, SSRIs are prescribed as a non-hormonal alternative to hormone therapy for women in menopause. The thought is that since estrogen increases serotonin levels (by increasing activity of tryptophan hydroxylase, the enzyme that produces serotonin from the amino acid tryptophan), perhaps this is a contributing factor in how estrogen decreases hot flashes. This makes sense, if you also consider the understood mechanism of action of migraines: serotonin release from the mast cells triggers initial vasoconstriction, followed by rebound vasodilation (which is the migraine). Hot flashes are also caused by vasodilation—so mediating serotonin levels may be helpful for the same reason, by creating a buffer that makes rebound action less extreme.
While this study shows that SSRIs can work, though, the effects are modest. It’s still not the whole story.
Natural Alternatives to Hormones
The mechanism by which hormones improve menopausal symptoms isn’t completely understood, but we know three possible components now: 1) they may increase the thermoneutral zone, or at least stabilize the blood vessels so they aren’t so hyperreactive; 2) they may stabilize the levels of catecholamines; or 3) they may stabilize serotonin levels. I haven’t seen any non-hormonal therapies that seem to operate on catecholamine concentrations; but here are those that fit into the other two categories, plus a few that don’t seem to fit elsewhere.
Action On Blood Vessels:
- Grape seed extract. This is the most promising possibility that I’ve seen in this category, due to this study. The active ingredient, proanthocyanidins, improve circulation by vasodilation (the blood vessels dilate). It’s therefore also good for coronary artery disease.
- Hesperidin. As far as I can tell, there’s only ever been one study on this, and it was done in conjunction with Vitamin C. This study shows that hesperidin, an extract of citrus rind, produces nitric oxide. This is a vasodilator as well.
- Magnesium. This study shows a 41.1% decrease in hot flash symptoms with magnesium. It’s not spectacular, but since magnesium is a vasodilator, that is the probable mechanism of action.
- Arginine? This is just speculation on my part, but if nitric oxide helps to stabilize blood vessels, and this is part of the mechanism of hot flashes (as this article suggests) then it might be worth a try.
Action on Serotonin:
- Dong quai/ Angelica sinensis. This herb is not a phytoestrogen; it has no estrogenic effects. It seems to work by increasing serotonin activity.
- Black cohosh. According to this study, black cohosh is not a phytoestrogen, but rather has serotonergic effects. But while this study implies that it is safe in women with a history of breast cancer, the jury is still officially out as to whether it has any estrogenic effects. Still, in my experience, it’s generally effective for more women than not.
- 5-HTP. This is the obvious choice if serotonin has any bearing on hot flashes, as it is the direct precursor for serotonin. While others have considered this as well, in this small study, it did not seem to work. Still, might be worth a try.
Many resources I found suggested Vitamin E, though this had mixed results and I couldn’t find a possible mechanism of action.
Others suggested flax seeds, as the lignans increase Sex Hormone Binding Globulin (SHBG). This means they can help balance hormones, though SHBG has a preference for testosterone first, and then estrogen. This might lower estrogen dominance relative to progesterone, and if it does work, this is likely the reason. But this study shows mixed results.
Evening Primrose Oil comes up a lot, but it too has mixed results. This study shows that it decreases severity of hot flashes, while this study shows that it doesn’t work at all. While EPO is a great essential fatty acid source, which will decrease inflammation, I’m not sure why this would have a direct effect on hot flashes. (It might have an indirect effect, though, since inflammation increases demand for cortisol, and thereby depletes progesterone.)
Finally, I have to throw out homeopathy as an option — and a really good one, if you choose the right remedy. This study shows that a well chosen remedy works well to decrease symptoms of hot flashes. And there’s definitely no estrogenic effects. The only down side: if you choose the wrong remedy, nothing happens at all.
Based on the data in the studies, as well as my clinical experience, Grape Seed Extract, Dong Quai, Black Cohosh, and individualized homeopathy are some of the best non-hormonal options for hot flashes.
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