Estrogen And Pots

[firewatcher]

I keep reading about the cardio-protective mechanisms of estrogen and how it is supposed to help with nitric oxide, etc. Then WHY is it that young, fertile, pre-menopausal women who are effected the most? If this is when our estrogen levels are supposed to be the highest, why does it hit us at that point in our lives?

I do feel better on supplemental hormones (estrogen and testosterone) but my hormones (gonadotropins) are unusually low. I have one endo who is telling me it is menopause, but my LH and FSH are not high enough to indicate that, they are barely high enough to indicate anything!

Any insights?

[juliegee]

Maybe because it's not steady. Don't we have the big drop right before out periods?

[sue1234]

I am almost the opposite. My FSH and LH go up into the 50s and I am told I am finally in menopause. At the same time, I am having my yearly period. So, thinking this is the last, ten months later now I have ANOTHER period. I've been doing this for the last 4 years.

I have one largish cyst on my remaining ovary and wonder if it is putting out too much progesterone. Progesterone is the hormone that keeps one from having a period, so I wonder. Maybe it is too much progesterone versus estrogen for me? I do have a growing facial hair problem.

I don't know. I was fine in my life until my periods became extremely wacky, and I went my whole adult life without being on birth control or any hormonal influence. Maybe estrogen/progesterone and their ratios play a part. I hope more people discuss this.

[Notgivinup]

I am so sick of going to the gyn. to get my hormones checked, and everything comes back NORMAL, perfect.

I'm 46 years old. I have terrible stomach pain with my period. I have major emotional swings right before, and before ovulation. I KNOW my hormones are messed up. But no doctor has ever been able to "catch" what is going on. It is soooo frustrating. I have also never been on any type of birth control.

I bought progesterone cream. I just don't know how or when to use it. Something is out of whack and I don't know what!

[erik]

What about men? If low-estrogen is bad then we are in dire straights!

[ramakentesh]

Especially me - ive always been a testosterone superman - side burns at 13, hairy chest by 15 and receding hair by 27 (just after POTS so can I blame that on POTS as well LOL)?

I dont know what my female hormones would be like - no doc in Aus will test that kind of thing - but I assume they are pretty normal.

[firewatcher]

Ah men, the dirty little hormonal secret is that YOU have estrogen too! Just like women have testosterone. You also have hormonal rhythms, they are just not as pronounced. Granted, you are all on the low-low side of the estrogen scale. But my question is WHY women? If estrogen is so neuro/cardio protective then why are we affected by POTS in a ratio of 5:1? I did not think that there was any hormonal pattern to all of us ladies, we seem to be all over the estrogen spectrum, yet we have a female intensive disorder. There is some correlation somewhere with estrogen since our symptoms fluctuate with their levels, but WHAT is the estrogen effecting?

[erik]

Ah men, the dirty little hormonal secret is that YOU have estrogen too!

Hmm. That might explain why I enjoy the movie Legally Blond so much. I knew there was a perfectly legitimate scientific reason.

Hormones are complex to say the least! Nitric oxide is ubiquitous as a signaler, messenger, transmitter & modulator in the nervous system so the precise where & how can't really be ignored. Sometimes a study is focused on a subset of POTS folks too... like low-flow in regard to the neuronal nitric oxide synthase thing.

When looking for inducers of "vascular permeability factor", I bumped in to this which shows estrogen influence (though they're looking at uterine specific action here, of course). In the context of POTS, such radical flux in endothelial & microvascular signals could be problematic, perhaps even if limited to selective uterine response or maybe it isn't that well contained always:

...rapid stimulation by estrogen correlates with estrogen-induced increases in uterine capillary permeability and growth

Anectdotally, it seems like stable (& extended low-hormone phase) are helpful for some folks. It's on some POTS treatment option lists, IIRC. Are there some studies directly of that treatment? There have to be tons of impacts of any hormone regime, but this baroreflex specific study is interesting since that autonomic response is implicated for some POTS:

Sympathetic Activity and Baroreflex Sensitivity in Young Women Taking Oral Contraceptives

I can't tell for sure which baroreflex changes might be advantageous and which might not. In theory, if hormones can adjust something like that it could at least explain some variation and perhaps a reason stability (or a particular influence) could be helpful.

Effect of estrogen on endothelial dysfunction in postmenopausal women with diabetes

The study states flatly that estrogen promotes nitric oxide release. There may be some more detail available to that, for example:

Prolactin and Estrogen Upregulate Carboxypeptidase-D to Promote Nitric Oxide Production and Survival of MCF-7 Breast Cancer Cells

...and to fight that...

Nitric Oxide Synthase Inhibition by L-NAME Inhibits Tumor-Induced Angiogenesis in Mammary Tumors

I wouldn't know if any of that has to do with neurons... from looking at what is said to regulate neuronal NO activity it seems it is different and general notions of NO may or may not apply. The endothelial vs neuronal roles are different, one being more of a messenger and the other a neuromodulator. All these substances play multiple different roles in different places (and NO is usually short lived & local intermediary). But it's interesting to see at least a detail of how estrogen interacts with NO in one locale.

[firewatcher]

In between the abstracts referring to decapitated rats and hot flashes, I found this tidbit:

Kardiol Pol. 2009 Mar;67(3):243-51.

Indices of autonomic nervous system activity in women with mild hypertension in the perimenopausal period.

Czarnecka D, Pośnik-Urbańska A, Kawecka-Jaszcz K, Kolasińska-Kloch W, Wojciechowska W, Fedak D.

Department of Cardiology and Hypertension, Jagiellonian University Medical College, Krakow, Poland. dczarnecka@interia.pl

Kardiol Pol. 2009 Mar;67(3):252-3.

BACKGROUND: Hypertension is more common after menopause. Increased incidence of hypertension can be attributed to autonomic nervous system dysfunction. The relationship between the parameters of heart rate variability (HRV), the levels of norepinephrine (NE) and leptin, and the menopausal status is still poorly understood, although there is some evidence suggesting distinct influence of estrogens on the above-mentioned indicators. AIM: To characterise the influence of menopause on indices of autonomic nervous system activity in women with mild hypertension. METHODS: We recruited 112 women aged 45 to 55 years with mild essential hypertension confirmed by 24 h ambulatory blood pressure monitoring. The study population was divided into two groups - postmenopausal (A, n = 61; age 51,03 +/- 1,39 years) and premenopausal (B, n = 51; age 50 +/- 2 years). None of the women had organ damage, other risk factors, inflammation diseases, were on estrogen replacement therapy or oral contraceptives. In all patients we assessed the leptin and NE levels. The HRV time-domain and spectral parameters were analysed from Holter ECG recordings. RESULTS: After menopause we observed, among others, the lower values of total power, VLF, HF (ms, %), LF (%) and LF:HF 24 h. The level of NE as well as the concentration of leptin were higher in postmenopausal rather than premenopausal women. CONCLUSION: Higher activity of sympathetic nervous system and higher levels of leptin in hypertensive women after menopause may suggest their participation in the pathogenesis of hypertension in this group of patients.

PMID: 19378230

[firewatcher]

Hypertension. 2008 Apr;51(4):1203-9. Epub 2008 Feb 7.

Hormonal influences on cardiovascular norepinephrine transporter responses in healthy women.

Moldovanova I, Schroeder C, Jacob G, Hiemke C, Diedrich A, Luft FC, Jordan J.

Medical University Charit?, Franz Volhard Clinical Research Center, Helios Klinikum Berlin and Max Delbr?ck Center for Molecular Medicine, Berlin, Germany.

Gender differences in human cardiovascular norepinephrine transporter function may be mediated through female sex hormones. We studied 16 healthy eumenorrheic women (25+/-1 years) during the early follicular phase (day 5+/-0) and midluteal phase (day 22+/-0) of the menstrual cycle. In a randomized, crossover, double-blind fashion, subjects ingested 8 mg of the selective norepinephrine transporter inhibitor reboxetine or placebo. We monitored heart rate, blood pressure, and thoracic bioimpedance at rest and during standard autonomic function tests, including head-up tilt. Venous estradiol and progesterone concentrations were higher in the luteal than in the follicular phase but did not differ between placebo and norepinephrine transporter inhibition testing days. On placebo, hemodynamics at rest and in response to different stressors were mostly identical between cycle phases. In the supine position, norepinephrine transporter inhibition increased blood pressure and stroke volume to a greater extent during the follicular than during the luteal phase. Conversely, the increase in heart rate and cardiac output with norepinephrine transporter inhibition was augmented in the luteal compared with the follicular phase. During head-up tilt with norepinephrine transporter inhibition, blood pressure and stroke volume decreased to a greater extent in the follicular than in the luteal phase. The tachycardic response to head-up tilt with norepinephrine transporter inhibition was augmented in the follicular phase. Our study suggests that sex hormones alter the hemodynamic response to norepinephrine transporter inhibition in women. The phenomenon may be explained by an effect of female sex hormones on norepinephrine transporter function, on compensatory cardiovascular responses, or both.

PMID: 18259012

[firewatcher]

Eur J Appl Physiol. 2009 Feb;105(3):381-6. Epub 2008 Nov 7.

Modulation of heart rate variability by estrogen in young women undergoing induction of ovulation.

Weissman A, Lowenstein L, Tal J, Ohel G, Calderon I, Lightman A.

Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa, Israel. wamir@netvision.net.il

Estrogens are involved in the modulation of the cardiovascular system, yet their effects in young women remains largely unknown. Women who undergo ovulation induction treatments attain extremely high estrogen concentrations during a very short time period. The aim of the present study was to evaluate the effects of an acute increase in estrogens on the autonomic nervous system modulation of heart rate variability (HRV). A total of 27 women undergoing ovulation induction and 14 normally menstruating women were prospectively studied. HRV was assessed during nadir and peak estrogen using time domain and power spectral density analyses. A significant increase in high-frequency spectral power (243 +/- 77 vs. 188 +/- 73 ms(2)/Hz, P < 0.01) with a significant decrease in the ratio of low to high-frequency power was observed during estrogen peak in women undergoing induction of ovulation. The acute increase in estrogen in women undergoing ovulation induction was associated with vagal activation and altered sympathovagal balance.

PMID: 18989692

Hypertension. 2008 Apr;51(4):1203-9. Epub 2008 Feb 7.

Hormonal influences on cardiovascular norepinephrine transporter responses in healthy women.

Moldovanova I, Schroeder C, Jacob G, Hiemke C, Diedrich A, Luft FC, Jordan J.

Medical University Charit?, Franz Volhard Clinical Research Center, Helios Klinikum Berlin and Max Delbr?ck Center for Molecular Medicine, Berlin, Germany.

Gender differences in human cardiovascular norepinephrine transporter function may be mediated through female sex hormones. We studied 16 healthy eumenorrheic women (25+/-1 years) during the early follicular phase (day 5+/-0) and midluteal phase (day 22+/-0) of the menstrual cycle. In a randomized, crossover, double-blind fashion, subjects ingested 8 mg of the selective norepinephrine transporter inhibitor reboxetine or placebo. We monitored heart rate, blood pressure, and thoracic bioimpedance at rest and during standard autonomic function tests, including head-up tilt. Venous estradiol and progesterone concentrations were higher in the luteal than in the follicular phase but did not differ between placebo and norepinephrine transporter inhibition testing days. On placebo, hemodynamics at rest and in response to different stressors were mostly identical between cycle phases. In the supine position, norepinephrine transporter inhibition increased blood pressure and stroke volume to a greater extent during the follicular than during the luteal phase. Conversely, the increase in heart rate and cardiac output with norepinephrine transporter inhibition was augmented in the luteal compared with the follicular phase. During head-up tilt with norepinephrine transporter inhibition, blood pressure and stroke volume decreased to a greater extent in the follicular than in the luteal phase. The tachycardic response to head-up tilt with norepinephrine transporter inhibition was augmented in the follicular phase. Our study suggests that sex hormones alter the hemodynamic response to norepinephrine transporter inhibition in women. The phenomenon may be explained by an effect of female sex hormones on norepinephrine transporter function, on compensatory cardiovascular responses, or both.

PMID: 18259012

Edited December 19, 2009 by firewatcher