ABSTRACT
Context:
Low-dose oral minoxidil (LDOM) can safely and effectively treat numerous hair disorders. Reported doses range from 0.25 mg to 5 mg daily titrated against clinical effectiveness and adverse events. Some clinicians advocate routine monitoring of patients treated with LDOM. However, there is limited evidence on whether minoxidil in such small doses adversely impacts patients with normal hemodynamic and biochemical baseline profiles.
Aims:
The aim of the study is to evaluate the need for regular monitoring of patients treated with LDOM.
Subjects and Methods:
This is a retrospective analysis of patients treated with LDOM in a tertiary hair clinic between April 2017 and June 2020. The clinical and laboratory parameters were assessed every 6 months. On commencing LDOM, baseline blood pressure, heart rate, and weight were recorded, and renal and liver function tests were performed.
Statistical Analysis:
The data were analyzed using graphical exploration.
Results:
The heart rate, weight, renal function, and liver function appeared stable throughout the treatment course. The weight and estimated glomerular filtration rate showed a trend to increase over time, but these findings were not statistically significant for any of the outcomes.
Conclusions:
The data support the position that routine monitoring is not required during treatment in asymptomatic patients with normal baseline values. Regular monitoring of blood pressure, heart rate, weight as well as liver and kidney function is not required during treatment with LDOM in patients with normal hemodynamic and biochemical baseline profiles. Patients with preexisting renal impairment can be prescribed oral minoxidil; however, we advocate ongoing monitoring in this subgroup, especially those with moderate-to-advanced disease. To the best of our knowledge, this is the first study that provides longitudinal monitoring data for LDOM with a follow-up period beyond 6 months and up to 36 months on treatment.
Keywords: Hair loss, low-dose oral minoxidil, monitoring, oral minoxidil
INTRODUCTION
Low-dose oral minoxidil (LDOM) is described in the literature to be well tolerated with only minor adverse effects. The most commonly reported side effect is hypertrichosis, which is usually mild and manageable. Other uncommon adverse effects are predictable relative to the timing of treatment and usually short-lived.[1,2,3,4] Nevertheless, the development of adverse effects is the main concern, creating advocacy for regular monitoring in patients treated with LDOM.[3] However, there is limited evidence on whether minoxidil in such small doses adversely impacts patients with normal hemodynamic and biochemical profiles. This study aimed at evaluating the need for regular monitoring of patients treated with LDOM.
SUBJECTS AND METHODS
This is a retrospective, single-center study reviewing patients diagnosed with different causes of hair loss treated with LDOM for more than 6 months. We reviewed all patients who attended our specialist hair clinic between April 2017 and June 2020, and we identified 115 patients who were prescribed LDOM. Those who had at least two documented visits 6 months apart were included in the study (n = 74). Data on the dose, concurrent medications, blood pressure (BP), heart rate, weight, laboratory investigations, and adverse effects were recorded. All patients were started on 0.625 mg daily, and then, the dose was increased according to their tolerance to a maximum of 5 mg daily. On commencing LDOM, baseline BP, heart rate, and weight were recorded, and renal and liver function tests were performed. The clinical and laboratory parameters were assessed during the review visits approximately every four to 6 months. In patients who developed adverse effects, the type of the effect and the need to adjust the dose of LDOM or withdraw it were also recorded. We used graphical exploration to analyze the collected data.
RESULTS
A total of 74 female patients, with a mean age of 45.8 (range 10–77), were included in the analysis with follow-up data up to 30 months on treatment. All recruited patients had normal baseline liver function tests. Twenty-seven patients had a reduced estimated glomerular filtration rate (eGFR) on baseline screening; the remaining patients had normal renal function tests.
We included patients with both nonscarring and scarring conditions, with the most frequent indication for use being female pattern hair loss (64.9%), persistent chemotherapy-induced alopecia (12.2%), alopecia areata (5.4%), fibrosing alopecia in a pattern distribution (5.4%), frontal fibrosing alopecia (4.1%), congenital hypotrichosis (2.7%), monilethrix (1.4%), central centrifugal cicatricial alopecia (1.4%), chronic telogen effluvium (1.4%), and traction alopecia (1.4%) [Table 1].
Table 1.
The participant’s mean age, oral minoxidil dosing regimen, concurrent systemic therapies, treatment-emergent adverse effects, hair conditions included in the study, and treatment discontinuation-related causes
| Characteristics | n=74, n (%) |
|---|---|
| Mean age | 45.8 |
| Oral minoxidil dose | |
| Dose started with 0.625 mg and remained on 0.625 mg | 13 (17.5) |
| Dose started with 0.625 mg then escalated during the study duration | 48 (65) |
| Dose of 1.25 mg | 35 |
| Dose of 2.5 mg | 11 |
| Dose of 5 mg | 2 |
| Dose started with 0.625 mg, maintained or escalated then discounted | 13 (17.5) |
| Maintained on 0.625 mg | 9 |
| Escalated dose to 1.25 mg | 4 |
| Treatment plan | |
| Monotherapy | 47 (63.5) |
| Concurrent or overlapping therapy | 27 (36.5) |
| Spironolactone | 9 |
| Finasteride | 2 |
| HCQ | 4 |
| MTX | 1 |
| Cyclosporine | 1 |
| Tetracycline antibiotics | 2 |
| Oral contraceptive pills | 3 |
| Spironolactone and finasteride | 2 |
| HCQ and doxycycline | 1 |
| HCQ and pioglitazone | 1 |
| HCQ and finasteride | 1 |
| Diagnosis | |
| Female pattern hair loss | 48 (64.9) |
| Postchemotherapy | 9 (12.2) |
| Alopecia areata | 4 (5.4) |
| Traction alopecia | 1 (1.4) |
| Chronic telogen effluvium | 1 (1.4) |
| Frontal fibrosing alopecia | 3 (4.1) |
| Fibrosing alopecia in pattern distribution | 4 (5.4) |
| Central centrifugal cicatricial alopecia | 1 (1.4) |
| Monilethrix | 1 (1.4) |
| Congenital hypotrichosis | 2 (2.7) |
| Adverse effect | n=34* |
| Hypertrichosis | 18 (24.3) |
| Dizziness | 8 (10.8) |
| Lower limb swelling | 4 (5.4) |
| Palpitation | 4 (5.4) |
| Headache | 2 (2.7) |
| Nausea | 2 (2.7) |
| Weight gain | 2 (2.7) |
| Chest tightness | 2 (2.7) |
| Rash | 1 (1.3) |
| Abdominal pain | 1 (1.3)† |
| Fever (was associated with palpitation) | 1 (1.3)‡ |
| Discontinuation of minoxidil therapy | n=13 |
| Chest tightness | 1 (1.3) |
| Skin rash | 1 (1.3) |
| Hair shedding | 1 (1.3) |
| Hypertrichosis | 1 (1.3) |
| Weight gain | 1 (1.3) |
| Palpitation‡ | 3 (4.1) |
| Pure palpitation | 1 |
| Associated with fever | 1 |
| Associated with weight gain | 1 |
| Dizziness | 3 (4.1) |
| Dizziness and headache | 1 |
| Dizziness and nausea | 1 |
| Dizziness and abdominal pain | 1 |
| Patient preference | 2 (2.7) |
| Flare of lupus | 1 |
| Sufficient cosmetic improvement | 1 |
*More than one symptom could be reported by the same patient; †Patient is on concurrent MTX therapy, 14 years old; ‡One case of palpitation was associated with fever. HCQ - Hydroxychloroquine; MTX - Methotrexate
Forty-seven (63.5%) patients were on minoxidil monotherapy, and 27 (36.5%) were treated with concurrent systemic therapies including spironolactone, finasteride, methotrexate, tetracycline antibiotics, hydroxychloroquine, pioglitazone, ciclosporin, and oral contraceptives. Most patients (65%) received LDOM at various incremental doses as tolerated; only 17.5% remained on the starting dose of LDOM (0.625 mg) without any increase. The duration of the treatment ranged from 6 to 36 months.
Treatment-emergent adverse events (TEAE) were reported by 34 patients (46%) [Table 1]. Hypertrichosis was the most common (n = 18, 24.3%), followed by dizziness (10.8%), lower limb edema (5.4%), palpitations (5.4%), headache (2.7%), nausea (2.7%), chest tightness (2.7%), weight gain (2.7%), rash (1.3%), and abdominal pain (1.3%). Eleven of 18 patients with TEAE experienced multiple adverse effects simultaneously [Table 1]. Twenty-three (67.7%) patients with TEAE were on minoxidil monotherapy, and 11 (32.3%) were treated with concurrent systemic therapies. All systemic adverse effects improved with the withdrawal of LDOM or dose adjustment. Hypertrichosis was well tolerated, necessitating no dose adjustment, except for one patient who discontinued therapy because she developed hypertrichosis without improvement in scalp hair density.
Thirteen patients (17.5%) discontinued the treatment; eleven due to side effects and two due to personal preference (flare-up of lupus and reaching satisfactory results). The most common reasons for discontinuation were dizziness (n = 3, 4.1%), which was associated with nausea, headache, and abdominal pain in three different patients, and palpitations (n = 3, 4.1%), which was the sole complaint in one patient but was associated with fever and weight gain in two others. Other adverse events leading to discontinuation of therapy include headache or nausea (n = 2), hypertrichosis (n = 1), weight gain (n = 1), hair shedding (n = 1), chest tightness (n = 1), and rash (n = 1). Most patients who discontinued the treatment had been treated with a dose of 0.625 mg (n = 8; 61.5%).
The mean arterial BP was stable in the first 24 weeks; however, toward the end of the study (30+ weeks), there was a slight reduction in mean arterial BP, the mean systolic BP (mSBP) reduced by 7 mmHg, and the mean diastolic BP (mDBP) reduced by 3 mmHg [Figures 1 and 2]. However, the reduction in both mSBP and mDBP was associated with a wide confidence interval. Further, none of the participants experienced any symptoms suggestive of hypotension.
Figure 1.

The mean systolic blood pressure was stable over time. SBP – Systolic blood pressure
Figure 2.

The mean diastolic blood pressure was stable over time. DBP – Diastolic blood pressure
The mean heart rate values were within the normal range during the entire treatment duration, there was however a wide confidence interval [Figure 3]. There was insufficient evidence to support any clinically relevant change in mean heart rate values. One participant developed palpitations, which were transient and not associated with an increased heart rate. Of note, the tachycardia associated with LDOM usually manifests during the first 1–3 days of treatment due to reflex sympathetic activation in response to the vasodilatory effect of oral minoxidil.[5] As we did not measure the heart rate during this period, this increase was not captured, as the goal of this study was to evaluate the longer-term impact of this medication.
Figure 3.

The mean heart rate values were within normal range
Weight measurements remained stable throughout the study. In five of six time points, the measurement of the mean weight values displayed no change [Figure 4]. The mean weight measurement at 24 weeks did increase, but these values were associated with a wide confidence interval and normalized at the subsequent reading.
Figure 4.

The mean weight values displayed no change. One spike in the measurement was associated with a wide confidence interval
The laboratory data related to the renal and liver function are presented in Table 2. No differences were observed between visits. The main laboratory variables appeared stable throughout the treatment course, only eGFR showing a nonsignificant trend to increase over time. Among those with low baseline eGFR (n = 27), four patients had an increase in their creatinine levels on treatment.
Table 2.
Contains the laboratory data related to the renal and liver function
| Month | ALT, mean (SD) | ALP, mean (SD) | Bilirubin, mean (SD) | Creatinine, mean (SD) | Urea, mean (SD) | eGFR, mean (SD) |
|---|---|---|---|---|---|---|
| 0 | 23.9 (9.9) | 76.5 (41.0) | 11.1 (9.9) | 63.4 (14.7) | 5.9 (5.4) | 81.6 (13.6) |
| 6 | 21.8 (7.7) | 72.8 (22.5) | 11.2 (11.4) | 64.9 (12.4) | 5.3 (1.4) | 80.5 (12.2) |
| 12 | 23.8 (18.8) | 74.6 (15.5) | 10.7 (7.2) | 66.1 (16.6) | 5.6 (1.2) | 78.5 (14.5) |
| 18 | 22.1 (8.1) | 74.5 (20.3) | 10.9 (6.0) | 64.7 (11.7) | 5 (0.95) | 80.1 (11.1) |
| 24 | 25.1 (10.7) | 79 (24.3) | 11.4 (6.5) | 62.4 (9.8) | 5.3 (0.66) | 85.3 (11.9) |
| 30 | 22.6 (8.3) | 70.3 (16.7) | 10.4 (5.7) | 61.7 (10.7) | 6.1 (1.03) | 87.8 (13.8) |
ALT - Alanine transaminase; ALP - Alkaline phosphatase; eGFR - Estimated glomerular filtration rate; SD - Standard deviation
DISCUSSION
LDOM was found to be well tolerated with a favorable safety profile in two systematic reviews and one large multicenter retrospective study.[4,5] Hypertrichosis (20%–24%) is the most frequently reported adverse effect, which seldom leads to treatment discontinuation.[1,5] Cardiovascular adverse effects, including postural hypotension, tachycardia, electrocardiogram changes, and lower limb edema, are relatively common with antihypertensive minoxidil doses (10–100 mg/day) but are minor and rare with LDOM.[5]
The overall frequency of adverse effects in our study was 45.9%. Hypertrichosis was by far the most common TEAE, yet among those who developed hypertrichosis (n = 18), only one patient stopped the treatment (5.5%). This suggests that, when present, minoxidil-induced increased facial and body hair growth is generally well tolerated. Discontinuation rates due to hypertrichosis are comparable with previous studies[1,5] and predominantly impact female patients.[5] Unfortunately, we were unable to directly compare hypertrichosis rates between our study and previous reports due to the way the data have been reported;[5] however, we speculate certain populations may tolerate this side effect better than others, with our northern European population generally coping well with this side effect. Further studies are needed to confirm whether the difference in skin types and hair colors might impact the tolerability of minoxidil-induced hypertrichosis.
Systemic adverse effects of LDOM, which occurred in 24.3% of patients, were mild and resolved with treatment discontinuation or dose reduction. Concurrent systemic therapies or coexisting illnesses might be responsible for some of these adverse effects. Three of eight patients who reported dizziness were also taking oral spironolactone and one patient who complained of nausea associated with dizziness was on hydroxychloroquine. The patient who developed abdominal pain was treated with methotrexate. Further, palpitations were reported by one patient who also described concurrent fever.
We found the BP measurement to be stable through the monitoring period, despite the slight reduction in mSBP more than mDBP at the end of treatment. A few studies have monitored BP during treatment with LDOM.[4,6] Three studies reported no variation in mean BP,[4,7] whereas most others demonstrated a slight but subclinical reduction in BP with LDOM therapy.[4,6,8,9,10] The reduction in mean change in systolic BP ranged from 0.5 to 4.5 mmHg,[9,11] whereas the reduction in mean diastolic pressure was between 1.1 mmHg and 6.5 mmHg.[8,9] Sanabria et al. monitored the BP at 24 weeks of LDOM with ambulatory BP monitoring. They found the mean arterial pressure to be slightly reduced at week 24 while awake, with no difference between the decrease in the systolic BP and diastolic reduction after 24 weeks of therapy.[10] Their findings were supported by Jimenez-Cauhe et al.[6] Together, these findings supported the hypothesis that LDOM has minimal or no hypotensive effect in normotensive patients. The authors of this study found that patients with high systolic BP (>130 mmHg) showed a greater reduction than those with normal systolic BP.[6]
The heart rate appeared to be stable throughout the treatment course. Two previous studies have recorded heart rate after 24 weeks; one study observed a slight increase in mean heart rate by 5 bpm,[8] whereas the other found no overall change in the mean heart rate on 24-h Holter monitoring by the end of treatment course.[6] A third study reported an increase in mean resting heart rate in only 6.5% of patients treated with LDOM.[12] Two of the participants developed palpitations; one after completing 44 months and the other one had a transient episode of palpitations that settled without dose adjustment. Both patients were receiving 1.25 mg of oral minoxidil and none of them had an associated increase in mean heart rate.
A recent study investigating the use of LDOM in patients with arrhythmias, including supraventricular extrasystole, atrial fibrillation, sinus tachycardia, cardiac syncope, and other unspecified arrhythmia, found LDOM to be very safe and well tolerated. None of the enrolled patients reported palpitations or worsening of their prior arrhythmia except one patient who reported supraventricular extrasystole, which resolved after dose reduction from 1 mg to 0.25 mg daily. None of these patients required modifying their prior medical treatment.[13]
A small number of studies reported weight gain as an adverse effect of LDOM[14,15] with some others examining the association between weight and development of adverse events.[5,10,16] To the best of our knowledge, our study appears to be the first to monitor weight over time with LDOM therapy, showing stable weight throughout the treatment period.
Our study found that renal and liver function to be stable throughout the treatment course, which is consistent with two previous reports that monitored biochemical profiles at baseline and after 24 weeks of treatment. The renal function and liver function tests displayed no relevant alterations.[8,10] The eGFR, both in patients with normal baseline values and in those with reduced baseline values, showed a trend to increase over time, although these findings were not statistically significant for any of the outcomes in both groups. Fifteen percent of patients with low baseline eGFR had worsening of the eGFR associated with increased creatinine level, although it remained within normal levels. An important cause of metabolic pericardial effusion and pericarditis is uremia. Although minoxidil-induced pericardial effusion and pericarditis are the most common among patients with advanced kidney disease or those on dialysis, it is reported to occur in approximately 3% of patients treated with a high dose of oral minoxidil.[5] Consistently with previous studies on LDOM, we encountered no serious cardiovascular adverse events, even in patients with impaired renal function. Nonetheless, caution is warranted in patients with advanced renal disease, given their higher risk of LDOM-induced pericarditis.[13] Further studies are needed to explore the impact of LDOM on eGFR in this group. Based on available data, we would advise caution with patients with renal impairment and advocate ongoing monitoring of the renal function in this cohort.
To the best of our knowledge, ours is the only study that has monitored patients on LODM for a prolonged period, beyond 6 months in duration, with this work providing data up to 30-month follow-up duration.
We suggest that monitoring BP, heart rate, and weight as well as renal and liver function is unnecessary in healthy asymptomatic individuals when doses of LDOM are administered (≤5 mg/day), which most of our patients were prescribed. Nonetheless, an individual’s monitoring schedule should be determined on a case-by-case basis based on a thorough history and assessment of risk, with a history of cardiovascular disease or renal impairment prompting closer monitoring.[17]
The main limitations of this study were its retrospective study design, single-center recruitment, and relatively small sample size. Further, comorbidities and coexisting systemic medication were not accounted for in the analysis.
CONCLUSIONS
These data support the position that regular monitoring is not required during treatment with LDOM in asymptomatic patients with normal baseline values. Our study is unique because it is the first study conducted on a UK population and provides longitudinal monitoring data with a follow-up period beyond 30 months. We recommend those with preexisting renal disease treated with LDOM are still monitored regularly during therapy.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Matthew Harries is supported by NIHR Manchester Biomedical Research Centre (NIHR203308).
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