Spironolactone for Women Over 65 with Androgenetic Alopecia

Spironolactone in Women over 65: How well does it work? What are the risks of hyperkalemia?

Spironolactone is a potassium sparing diuretic. There is a theoretical risk for elevated potassium (hyperkalemia) in patients who use this drug. Prior studies in patients using the drug for acne have not found an increased risk of hyperkalemia for women under 40 years of age.

An important group to study the use and effectiveness of spironolactone is women over 65. There is a theoretical concern that hyperkalemia could become an issue in women in the 60s, 70s and 80s on account of declining renal function that increases the risk of hyperkalemia. Furthermore, the use of certain medications, including ACE inhibitors and angiotensin receptor inhibitors, could further increase the chances of women developing hyperkalemia.

Collins et al, 2023

Authors set out to retrospectively evaluate the incidence of incidence of hyperkalaemia within the first year of using spironolactone. In this study, hyperkalemia was defined as a serum potassium greater than 5.0 mEq/L

There were 87 women with FPHL who were above age 65. The average age was 71 and the range was 66-80. 41.4% of patients had a prior diagnosis of hypertension, 33 % had a prior diagnosis of cardiovascular disease and 25 % had renal disease.

42.5% of these patients were prescribed a potassium-sparing medication, which included angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs). No patients were taking other antiandrogen medications.

Spironolactone doses ranged between 12.5 mg and 200 mg daily; 50% of patients were prescribed just 25 mg once daily. The average serum potassium value increased from 4.2 mEq/L at the start of treatment to 4.4 after 1 year of use. The average creatinine increased from 0.84 mg/dL (74.3 umol/L) to 1.2 mg/dL  (106.1 μmol/L).  

9 of the 87 patients (10.3%) developed hyperkalemia. Patients with a serum potassium ≥ 4.6 mEq/L had an almost 10 fold greater risk to develop hyperkalemia (relative risk (RR) 9.5, P=0.002, 95% confidence interval (CI) 2.92–30.89]. Patients with a serum creatinine above 0.89 mg/dL (78.7 μmol /L) had a nearly 3.5 fold increased risk of developing high potassium.

Of the patients with hyperkalaemia, 63% were prescribed a daily dose of spironolactone of 50 mg or higher and 37 % were prescribed a dose of just 12.5 mg or 25 mg. 36 of the 37 patients who were prescribed ARB/ACE did not develop hyperkalemia. Only one patient who was prescribed a combined ACE inhibitor/ARB medication developed hyperkalemia.

Although there were 9 patients that had hyperkalemia, there was really only one patient that had persistently elevated serum potassium levels that required spironolactone dose reduction or discontinuation. Only one patient with hyperkalemia reported symptoms (leg cramps). There were no cases of cardiac arrhythmia in any patients.

How well did the spironolactone work?

The Sinclair scale improved about 0.5 a point after 12 months of treatment. The average initial Sinclair grade was 2.4 (range 1–5) and the average Sinclair grade after 12 months of treatment with spironolactone was 1.8 (range 1–3). The average grade change after 12 months was +0.5, reflecting modest hair improvement growth.

Interestingly, the authors showed that there was no significant difference in Sinclair grade improvement with different spironolactone doses [one way ANOVA, P=0.09].  

Summary

This is a small study which suggests that low doses of spironolactone are effective for women with AGA over 65 years of age and that persistent hyperkalemia from use of the drug is rare. Overall, just 1 patient (1.1% of the group) had persistently elevated potassium levels.

This is similar to the data from Plante et al in 2022 that found that 0.5% of 195 women using oral spironolactone had persistently elevated potassium levels.

All in all, the authors here propose that starting at 25 mg daily may be a good idea given their concerns about an increased risk for hyperkalemia at doses 50 mg and above. The authors propose that these low doses may still be quite effective give that they did not observe any significant difference in Sinclair grade improvement with higher doses compared to lower doses.

Although this data suggests that low doses of spironolactone are effective, I’m not sure I’m completely convinced but it sure is interesting. I rarely use such low doses so perhaps it’s something to consider in the future. More studies are needed of low dose spironolactone. It does seem that small improvements can occur with oral spironolactone in women over 65 years of age …. but it’s generally mild (0.5 points on the Sinclair scale).

This study also suggests that 97% of women who use ARB and ACE blood pressure medications will not develop hyperkalemia with spironolactone. These are encouraging data and suggest that women with androgenetic alopecia who use these medications may not automatically be excluded from spironolactone use – one simply needs to monitor potassium levels more frequently.

The data in the Collins et al study are somewhat at odds with the systematic review in 2022 by James et al. James et al set out to comprehensively examine all prior studies of spironolactone use for treating AGA. In total, the authors reviewed a total of 12 studies with 286 participants. Patients in these studies were treated with spironolactone at doses ranging between 25 mg and 200 mg for a duration of 6 months to 4 years. According to the authors, spironolactone seemed best at doses 100-200 mg. James et al stated that  spironolactone was largely ineffective in studies where the dosage was below 100 mg.

This study by Collins et al suggests that spironolactone bumps the potassium by about 0.2 mEq/L and the creatinine by about 0.4 mg/dL (40 umol/L). I think this is really important as  we do see mild renal impairment like this with spironolactone in our slightly older patients. We’ve even occasionally had some patients see nephrology (kidney specialists) to get a better sense of how to manage this sort of mild renal impairment.

All in all, this is a valuable study of spironolactone use in patients over 65. I don’t think the debate is truly over as to what dose of spironolactone works best! But it’s becoming clear that risks of persistent hyperkalemia is quite low. This study does not change the general view that all women over 45 who use spironolactone should have blood tests to monitor for potassium. Women found to have elevated potassium, should first and foremost have their potassium levels rechecked within 1 week.  Many of these patients will be found to have normal potassium levels when it’s checked again.

REFERENCE

Collins MS, et al. Retrospective analysis of the risk of hyperkalaemia in women older than 65 years of age prescribed sprionolactone for female-pattern hair loss. Br J Dermatol. 2023 Feb 22;188(3

Plante et al. The Need for Potassium Monitoring in Women on Spironolactone for Dermatologic ConditionsJ Am Acad Dermatol. 2022 Jan 21;S0190-9622(22)00081-0.