Menstrual Cycle Affects Renal-Adrenal and Hemodynamic Responses During Prolonged Standing in the Postural Orthostatic Tachycardia Syndrome
Open accessAbstract
Approximately 500 000 American premenopausal women have the postural orthostatic tachycardia syndrome (POTS). We tested the hypothesis that in POTS women during orthostasis, activation of the renin-angiotensin-aldosterone system is greater, leading to better compensated hemodynamics in the midluteal phase (MLP) than in the early follicular phase of the menstrual cycle. Ten POTS women and 11 healthy women (controls) consumed a constant diet 3 days before testing. Hemodynamics and renal-adrenal hormones were measured while supine and during 2-hour standing. We found that blood pressure was similar, heart rate and total peripheral resistance were greater, and cardiac output and stroke volume were lower in POTS subjects than in controls during 2-hour standing. In controls, hemodynamic parameters were indistinguishable between menstrual phases. In POTS subjects, cardiac output and stroke volume were lower and total peripheral resistance was greater in the early follicular phase than MLP after 30 minutes of standing; however, blood pressure and heart rate were similar between phases. Plasma renin activity (9±6 [SD] versus 13±9 ng/mL per hour; P =0.04) and aldosterone (43±22 versus 55±25 ng/dL; P =0.02) were lower in the early follicular phase than MLP in POTS subjects after 2 hours of standing. Catecholamine responses were similar between phases. The percentage rate of subjects having presyncope was greater in the early follicular phase than MLP for both groups (χ 2 P <0.01). These results suggest that the menstrual cycle modulates the renin-angiotensin-aldosterone system and affects hemodynamics during orthostasis in POTS. The high estrogen and progesterone in the MLP are associated with greater increases in renal-adrenal hormones and presumably more volume retention, which improve late-standing tolerance in these patients.
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Changes in estrogen and its effects on the renin-angiotensin-aldosterone system might contribute to the lightheadedness reported in POTS.
“These data support our hypothesis that changes in estrogen and its effects on the RAAS might contribute to the lightheadedness reported in POTS.”
From Gynecologic disorders and menstrual cycle lightheadedness in postural tachycardia syndrome (2012) · cites this paper as [21]
The Results (EFP versus MLP; page unavailable) report more presyncope when both estrogen and progesterone were low, alongside lower renin activity and aldosterone. The Discussion (Menstrual Cycle Effects in POTS Women; page unavailable) links menstrual phase to RAAS responses but says estrogen’s specific effect is uncertain; the study does not isolate an estrogen–RAAS pathway to lightheadedness. (LLM, conf=0.83)
Experimental — accuracy not yet measuredWomen with POTS often report fluctuations in the severity of POTS symptoms throughout their menstrual cycle, with worsening during either the pre-menstrual or early follicular phase when both estrogen and progesterone levels are dropping or low.
“Women with POTS often report fluctuations in the severity of POTS symptoms throughout their menstrual cycle, with worsening during either the pre-menstrual or early follicular phase when both estrogen and progesterone levels are dropping or low (6,9,45,51).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [45]
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Experimental — accuracy not yet measuredIn POTS patients, cardiac output and stroke volume were lower, and total peripheral vascular resistance higher, during the early-follicular phase.
“However, in POTS patients, cardiac output and stroke volume were lower, and total peripheral vascular resistance higher, during the early-follicular phase.”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [45]
The Results (EFP versus MLP; page not provided) report lower cardiac output and stroke volume and greater total peripheral resistance in POTS women during the early-follicular phase than the mid-luteal phase. The claim omits the condition that these differences appeared only after 30 minutes of standing; supine measurements and responses during the initial 30 minutes did not differ between phases. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThere appear to be fluctuations in the renin-angiotensin-aldosterone system during different phases of the menstrual cycle that affect the orthostatic hemodynamic response in POTS.
“There also appear to be some fluctuations in the renin-angiotensin-aldosterone system during different phases of the menstrual cycle that affect the orthostatic hemodynamic response in POTS (45).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [45]
When plasma volume, blood volume, and supine hemodynamics were measured in a cohort of POTS patients and controls, no variations were noted while comparing the mid-luteal phase to the early-follicular phase.
“When plasma volume, blood volume, and supine hemodynamics were measured in a cohort of POTS patients and controls, no variations were noted while comparing the mid-luteal phase to the early-follicular phase (45).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [45]
Some POTS patients with hypovolemia have inappropriately low standing plasma renin activity and aldosterone compared with normovolemic controls.
“Some POTS patients with hypovolemia, however, have inappropriately low standing plasma renin activity and aldosterone compared with normovolemic controls [46;12].”
From Postural tachycardia syndrome: beyond orthostatic intolerance (2015) · cites this paper as [12]
A significant portion of POTS patients suffer from a state of persistent hypovolemia.
“A significant portion of POTS patients suffer from a state of persistent hypovolemia.”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [33]
Some POTS patients have 13-22% less plasma or blood volume than healthy controls.
“Studies have shown that some POTS patients have 13-22% less plasma or blood volume than do healthy controls (33-35).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [33]
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References 43 · Cited by 62
- Authors
- Fu, Q., VanGundy, T. B., Shibata, S., Auchus, R. J., Williams, G. H., & Levine, B. D.
- Affiliations
- Brigham and Women's Hospital (US)
- Venue
- Hypertension
- Published
- 2010-07
- Volume
- 56
- Issue
- 1
- Pages
- 82-90
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC2894615
- OpenAlex
- W2155549071
- Cited by
- 62
- References
- 43
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 1 · 2020: 10 · 2019: 5 · 2018: 4 · 2017: 1 · 2016: 1 · 2015: 4 · 2014: 4 · 2012: 8
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL075283, K23HL075283)
- National Cancer Institute (CA00701)
- National Center for Research Resources (RR 00633, M01RR000633)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- postural orthostatic tachycardia syndrome, menstrual cycle, mid-luteal phase, follicular phase, renin-angiotensin-aldosterone system, plasma renin activity, aldosterone, catecholamines, orthostatic tolerance, hemodynamics, cardiac output, stroke volume, systemic vascular resistance, presyncope, estrogen and progesterone, volume retention
- MeSH terms
- Adult, Aldosterone, Catecholamines, Chromatography, High Pressure Liquid, Estradiol, Female, Hemodynamics, Humans, Menstrual Cycle, Progesterone, Radioimmunoassay, Renin, Retrospective Studies, Texas, Incidence, Postural Orthostatic Tachycardia Syndrome
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