What causes hotflashes.
Posted: Sun Aug 08, 2021 1:30 pm
Hot flashes are a sign of very low T. But it is not clear what is the mechanism that causes it and how it is possible to reduce or eliminate it.
In menopausal women, this phenomena is more studied, as the problem is general and massive. As there is no big difference in this aspect between male or female body chemistry, then studies done on women hot flashes apply to male hot flashes as well.
This work was published in 2013. I am not aware if there are developements in that area.
MENOPAUSAL HOT FLASHES: MECHANISMS, ENDOCRINOLOGY, TREATMENT
Robert R. Freedman, Ph.D.
Here I quote most interesting parts of it:
_____________________
Since HFs (HotFlash) occur in the vast majority of women having natural or surgical menopause, estrogens are clearly involved in their etiology. This is consistent with the fact that estrogen therapy virtually eliminates HFs. However, estrogen reduction alone does not explain the occurrence of HFs because there are no relationships between these symptoms and plasma, urinary, or vaginal [20] levels of estrogens, nor are there differences in plasma levels between women with and without HFs [9,20]. Additionally, clonidine reduces HF frequency but does not change estrogen levels [21], and prepubertal girls have low estrogen levels but no HFs.
-----------------------------
The main point here is that prepubertal girls do not have hotflashes despite their estrogen levels are low.
_____________________
Therefore, estrogen withdrawal is necessary but not sufficient to explain the occurrence of HFs. A temporal relationship was observed between HFs and luteinizing hormone (LH) pulses [22,23]. However, further work demonstrated that women with isolated gonadotropin deficiency had HFs but no LH pulses [24], and those with hypothalamic amenorrhea had LH pulses but no HFs. Also, HFs occur in women with LH suppression from GnRH compounds [25,26], in women with pituitary insufficiency and hypoestrogenism [27], and in hypophysectomized women, who have no LH pulses [28].
-----------------------------
HotFlashes are not related to pulses of GnRH, LH or FSH.
_____________________
Thus, we believe that hot flashes are triggered by Tc (Body core temperature) elevations acting within a greatly narrowed thermoneutral zone in postmenopausal women with HFs. A HF, consisting of sweating and peripheral vasodilation, is provoked when Tc reaches the upper threshold. Tc then declines, and when the lower threshold is crossed, shivering occurs. What biochemical mechanisms account for this?
Basic science investigations have found that increased brain norepinephrine (NE) narrows the width of the thermoneutral zone [31]. Conversely, clonidine lowers NE release, raises the sweating threshold, and reduces the shivering threshold. We therefore hypothesize that increased brain NE narrows the thermoneutral zone in menopausal women with HFs.
We determined the Tc sweating threshold in women with and without HFs during I.V. clonidine and placebo [45]. We showed that clonidine significantly elevated the sweating threshold compared to placebo in the women with HFs, whereas, the opposite occurred in the women without HFs. We therefore believe that clonidine reduces HFs by raising the Tc sweating threshold.
We then conducted a similar study to examine the mechanism through which estrogen ameliorates HFs [46]. Symptomatic menopausal women were randomly assigned to receive 1 mg/day 17 β-estradiol P.O. or placebo for 90 days. We found that the Tc sweating threshold was significantly elevated and HF frequency significantly ameliorated in the E2 but not the placebo group. Thus, estrogen ameliorates HFs by raising the Tc sweating threshold, but we do not know the precise mechanisms of this.
-----------------------------
_____________________
8.2.2 Clonidine
As noted earlier, clonidine ameliorates HFs by widening the thermoneutral zone. Two small placebo-controlled studies found that clonidine P.O. reduced HF frequency by 46% and transdermal clonidine reduced it by 80% [58]. Two studies of breast cancer survivors receiving tamoxifen showed smaller, but significant reductions in HF frequency for oral [59] and transdermal clonidine [60] compared with placebo. Side effects of clonidine include hypotension, dry mouth, and sedation [61].
-----------------------------
Clonidine could be one of the solutions against HF's for people who do not want sex steroids.
Full text and graphs are available here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612529/
In menopausal women, this phenomena is more studied, as the problem is general and massive. As there is no big difference in this aspect between male or female body chemistry, then studies done on women hot flashes apply to male hot flashes as well.
This work was published in 2013. I am not aware if there are developements in that area.
MENOPAUSAL HOT FLASHES: MECHANISMS, ENDOCRINOLOGY, TREATMENT
Robert R. Freedman, Ph.D.
Here I quote most interesting parts of it:
_____________________
Since HFs (HotFlash) occur in the vast majority of women having natural or surgical menopause, estrogens are clearly involved in their etiology. This is consistent with the fact that estrogen therapy virtually eliminates HFs. However, estrogen reduction alone does not explain the occurrence of HFs because there are no relationships between these symptoms and plasma, urinary, or vaginal [20] levels of estrogens, nor are there differences in plasma levels between women with and without HFs [9,20]. Additionally, clonidine reduces HF frequency but does not change estrogen levels [21], and prepubertal girls have low estrogen levels but no HFs.
-----------------------------
The main point here is that prepubertal girls do not have hotflashes despite their estrogen levels are low.
_____________________
Therefore, estrogen withdrawal is necessary but not sufficient to explain the occurrence of HFs. A temporal relationship was observed between HFs and luteinizing hormone (LH) pulses [22,23]. However, further work demonstrated that women with isolated gonadotropin deficiency had HFs but no LH pulses [24], and those with hypothalamic amenorrhea had LH pulses but no HFs. Also, HFs occur in women with LH suppression from GnRH compounds [25,26], in women with pituitary insufficiency and hypoestrogenism [27], and in hypophysectomized women, who have no LH pulses [28].
-----------------------------
HotFlashes are not related to pulses of GnRH, LH or FSH.
_____________________
Thus, we believe that hot flashes are triggered by Tc (Body core temperature) elevations acting within a greatly narrowed thermoneutral zone in postmenopausal women with HFs. A HF, consisting of sweating and peripheral vasodilation, is provoked when Tc reaches the upper threshold. Tc then declines, and when the lower threshold is crossed, shivering occurs. What biochemical mechanisms account for this?
Basic science investigations have found that increased brain norepinephrine (NE) narrows the width of the thermoneutral zone [31]. Conversely, clonidine lowers NE release, raises the sweating threshold, and reduces the shivering threshold. We therefore hypothesize that increased brain NE narrows the thermoneutral zone in menopausal women with HFs.
We determined the Tc sweating threshold in women with and without HFs during I.V. clonidine and placebo [45]. We showed that clonidine significantly elevated the sweating threshold compared to placebo in the women with HFs, whereas, the opposite occurred in the women without HFs. We therefore believe that clonidine reduces HFs by raising the Tc sweating threshold.
We then conducted a similar study to examine the mechanism through which estrogen ameliorates HFs [46]. Symptomatic menopausal women were randomly assigned to receive 1 mg/day 17 β-estradiol P.O. or placebo for 90 days. We found that the Tc sweating threshold was significantly elevated and HF frequency significantly ameliorated in the E2 but not the placebo group. Thus, estrogen ameliorates HFs by raising the Tc sweating threshold, but we do not know the precise mechanisms of this.
-----------------------------
_____________________
8.2.2 Clonidine
As noted earlier, clonidine ameliorates HFs by widening the thermoneutral zone. Two small placebo-controlled studies found that clonidine P.O. reduced HF frequency by 46% and transdermal clonidine reduced it by 80% [58]. Two studies of breast cancer survivors receiving tamoxifen showed smaller, but significant reductions in HF frequency for oral [59] and transdermal clonidine [60] compared with placebo. Side effects of clonidine include hypotension, dry mouth, and sedation [61].
-----------------------------
Clonidine could be one of the solutions against HF's for people who do not want sex steroids.
Full text and graphs are available here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612529/
