To the Editor:
Spironolactone is a mineralocorticoid receptor antagonist and potassium-sparing antihypertensive, typically dosed at 25–100mg/day, that is used off-label for several dermatologic conditions in women1. A 2010 Cochrane Review found dose response relationship between spironolactone and blood pressure (BP) ≤50mg/day in patients with primary hypertension, but not >50mg/day.2 Santer et. al, in a phase III multicenter double-blind randomized controlled trial of women taking spironolactone (50–100 mg/day) vs. placebo for acne treatment, found that rates of hypotensive symptoms were similar between groups (P=0.07)3. Therefore, we investigated whether women taking spironolactone for acne, hair loss, and/or hirsutism developed hypotension.
Demographics, and BP measurements from females taking spironolactone for dermatologic conditions, 2006–2021, were collected. R Version 4.2.2 was used, with Fisher’s Exact, Wilcoxon rank sum, and Pearson’s Chi-squared tests with significance P<0.05 (Mendeley Supplemental Material).
A total of 2,084 patients taking ≥1 course of spironolactone was screened. Those with baseline (≤90 days before course start date) and ≥1 follow-up BP measurements were included (n=1,173). Only 3.1% (n=36) experienced absolute hypotension. Age group, race, ethnicity, and maximum daily dose were similar among patients with and without absolute hypotension during treatment (all P>0.05) (Table 1). Of hypotensive patients, 5.5% (n=2) had their dose decreased, and 2.8% (n=1) discontinued spironolactone.
Table 1:
Patient Characteristics
| Hypotension Status | ||||
|---|---|---|---|---|
| Patient characteristics | Overall, N=1,173 | No, N=1,137 | Yes, N=36 | p-value1 |
| Age on course start date | 0.2 | |||
| Median (IQR) | 29 (25,35) | 29 (25,35) | 30 (26,41) | |
| Mean (SD) | 32 (10) | 32 (10) | 34 (11) | |
| Range | 18,76 | 18,76 | 19,63 | |
| Age Group, n(%) | 0.3 | |||
| <25 | 252 (21%) | 244 (21%) | 8 (22%) | |
| 25–34 | 604 (51%) | 589 (52%) | 15 (42%) | |
| 35–44 | 194 (17%) | 188 (17%) | 6 (17%) | |
| 45 or older | 123 (10%) | 116 (10%) | 7 (19%) | |
| Race Groups, n(%) | 0.5 | |||
| Asian | 88 (9.0%) | 84 (8.8%) | 4 (13%) | |
| Black/African American | 77 (7.9%) | 75 (7.9%) | 2 (6.7%) | |
| Other | 146 (15%) | 140 (15%) | 6 (20%) | |
| White | 669 (68%) | 651 (69%) | 18 (60%) | |
| Ethnic Groups, n(%) | 0.4 | |||
| Hispanic/Latin/Spanish Origin | 142 (15%) | 136 (15%) | 6 (21%) | |
| Not Hispanic/Latin/Spanish Origin | 786 (85%) | 763 (85%) | 23 (79%) | |
| Max Daily Dose | 0.4 | |||
| Median (IQR) | 100 (50,100) | 100 (50,100) | 100 (50,100) | |
| Mean (SD) | 88 (39) | 88 (39) | 94 (43) | |
| Range | 12, 225 | 12, 225 | 25, 200 | |
| Max Daily Dose Group, n(%) | 0.6 | |||
| ≤50 | 418 (36%) | 407 (36%) | 11 (31%) | |
| 75–100 | 638 (54%) | 618 (54%) | 20 (56%) | |
| 125–200 | 117 (10.0%) | 112 (9.9%) | 5 (14%) | |
| Indication, n(%) | 0.044 | |||
| Acne | 693 (59%) | 678 (60%) | 15 (42%) | |
| Hair Loss | 185 (16%) | 180 (16%) | 5 (14%) | |
| Hirsutism | 113 (9.6%) | 108 (9.5%) | 5 (14%) | |
| Multiple Indications* | 182 (16%) | 171 (15%) | 11 (31%) | |
Wilcoxon rank sum test; Fisher’s exact test; Pearson’s Chi-squared test
Includes combination of acne, hair loss, and/or hirsutism
There was no change in systolic or diastolic BP when stratified by maximum daily dose or age group (all P>0.05) (Mendeley Supplemental Table 1). Using linear regression, spironolactone dose, age, race/ethnicity, and indication were not associated with mean change in systolic BP from baseline to first follow up (all P>0.05) (Mendeley Supplemental Table 2).
We found that rates of absolute hypotension and clinically significant hypotension requiring therapy change were 3.1% and 0.26%, respectively. Patient demographics were similar among women who developed vs. did not develop hypotension. Our findings are similar to retrospective studies of 403 women taking spironolactone for acne, with 267 patients having 3.5 mm Hg mean systolic BP decrease (95% CI, 2.0–4.9) and 100 women taking 0.25 mg of oral minoxidil and 25 mg spironolactone for androgenic alopecia experiencing 4.52 mmHg mean systolic BP decrease (no p-value reported), with 2 women experiencing postural hypotension4,5. Women in our study took spironolactone ≤50–200 mg/day, similar to doses that improved Acne-Specific Quality of Life scores in the Santer et. al’s study.3
Limitations include retrospective design, majority white individuals, lack of co-morbidity analysis, some patients taking relatively low spironolactone doses, and lack of information about orthostatic symptoms experienced by patients with systolic BP>90.
In summary, we found a 0.26% rate of hypotension requiring therapy change and no changes in mean systolic or diastolic BP with spironolactone treatment for dermatologic conditions. Age, race, ethnicity, and maximum daily dose were not useful or reliable predictors of patients at risk of developing absolute hypotension or significant BP decreases while taking spironolactone for dermatologic conditions. Therefore, we recommend measuring baseline BP prior to initiating spironolactone therapy. Continuous BP monitoring may not be required for patients taking spironolactone for dermatologic indications without orthostatic symptoms. Prospective studies are needed to confirm that hypotension is unlikely with spironolactone treatment.
Funding sources:
This investigation was supported by the National Center for Advancing Translational Sciences (NCATS) grant # UL1-TR-002384 of the Clinical and Translational Science Center at Weill Cornell Medical College.
Footnotes
Conflicts of Interest: Ms. Hill, Dr. Wang, Mr. Shaikh, Mr. Ong, Dr. Christos, and Dr. Lipner have no conflicts of interest.
Financial Disclosures: Dr. Lipner has served as a consultant for Ortho-Dermatologics, Eli Lilly, Moberg Pharmaceuticals, and BelleTorus Corporation.
IRB approval status: Reviewed and approved by Weill Cornell Medicine IRB; protocol # 19-11021077
Reprint requests: No reprints requested.
Patient consent: Not applicable
Supplemental material: https://data.mendeley.com/datasets/8mzr23hy7y/1
This work has not been previously published
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