THERAPEUTICS D O I 1 0 .1 1 1 1 / j . 1 3 6 5 - 2 1 3 3 . 2 0 0 8 . 0 8 4 7 6 .

Topical glycopyrrolate for patients with facial hyperhidrosis

W.O. Kim, H.K. Kil, K.B. Yoon and D.M. Yoon
Department of Anaesthesiology and Pain Medicine, Anaesthesia and Pain Research Institute, Yonsei University College of Medicine, CPO Box 8044, Seoul, Korea

Summary

Correspondence Background Facial hyperhidrosis may negatively impact the quality of life. Although
Won Oak Kim. various conservative modalities have been suggested, the condition is not often
E-mail: wokim@yumc.yonsei.ac.kr; treated successfully.
drwokim@hanmail.net
Objectives To examine whether topical glycopyrrolate could be an effective and safe
Accepted for publication treatment for facial hyperhidrosis.
4 November 2007 Methods Twenty-five patients with facial hyperhidrosis were enrolled and treated
with 2% topical glycopyrrolate on one half of the forehead while the other half
Key words of the forehead was treated with a placebo.
craniofacial, forehead hyperhidrosis, gustatory,
Results The sweat production rate of the half of the forehead treated with topical
topical glycopyrrolate
glycopyrrolate was significantly reduced to 37Æ6 ± 2Æ8 mg min)1 (mean ± SEM)
Conflicts of interest compared with 102Æ2 ± 5Æ5 mg min)1 at the placebo-treated half of the forehead
None declared. (P < 0Æ001). Patients evaluated their degree of anhidrosis as excellent in six
(24%) patients, good in 16 (64%), fair in two (8%) and poor in one (4%).
Twenty-four patients (96%) were partially or fully satisfied with their fair to
excellent anhidrosis; only one patient (who developed a transient headache after
treatment) was dissatisfied with its therapeutic effect. Only seven patients (28%)
experienced recurrence within 1 day while 17 patients (68%) had recurrence
within 2 days. One patient (4%) remained stable for up to 4 days.
Conclusions Topical glycopyrrolate application appears to be effective and safe for
the treatment of excessive facial sweating in primary craniofacial and secondary
gustatory hyperhidrosis following sympathectomy.

Focal facial hyperhidrosis is caused by excessive eccrine sweat
gland secretion, leading to a socially debilitating condition
which, in its severest form, can significantly impair quality of
life. Although excessive facial sweating is rare and is not
usually a cause of major morbidity, patients suffer from many
disadvantages that might be overshadowed by palmar, plantar
and axillary hyperhidrosis.
Craniofacial hyperhidrosis is a primary condition. It is a dis-
order of sudomotor regulation and is triggered by heat and
stressful stimuli.1 Gustatory hyperhidrosis is a related disorder
that is usually a secondary symptom of thoracic sympathec-
tomy, diabetes, or removal of the parotid gland, and is associ-
ated with eating food, thinking of food, and is especially
worsened by spicy food.2,3 The features of excessive and local-
ized sweating on the scalp, forehead, nose and upper lip are
similar in both forms of hyperhidrosis when a sensitive situa-
tion occurs.
Treatments for facial sweating include thoracic sympathec-
tomy (although it is not widely recommended in primary
hyperhidrosis), topical application of anticholinergic drugs or
aluminium chloride, oral medications, and injection of botu-
linum toxin. Among these treatment choices, topical anticho-
linergic agents, such as glycopyrrolate, have been reported to
be effective in managing the facial sweating of craniofacial
and gustatory hyperhidrosis.3–6 Therefore, we investigated the
efficacy, side-effect profile, and patients’ preferences for topi-
cal glycopyrrolate in focal facial sweating.
Patients and methods
We studied 25 patients who were being treated for severe
facial sweating at the Hyperhidrosis Clinic at Severance Hospi-
tal of Yonsei University Health System from May 2005 to July
2006. No patients were excluded from the analysis. Seventeen
patients were male and eight were female. The mean age was
30Æ4 ± 4Æ3 years and mean duration of facial sweating was
10Æ3 ± 2Æ3 years for 19 patients with craniofacial hyperhidro-
sis. All six patients who had gustatory hyperhidrosis had had
T2–3 thoracic sympathectomy 10–45 months previously.
We used 2% topical glycopyrrolate pads (http://www.
pharmacy.ca; SecureTM, Toronto, ON, Canada) in this study.3
The use of 1Æ5% or 2% on the face prevents possible systemic
side-effects, while > 2% concentration is appropriate for the
hyperhidrosis of other sites of the body, palms and soles. The

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1094 Journal Compilation  2008 British Association of Dermatologists • British Journal of Dermatology 2008 158, pp1094–1097

procedures were performed at an outpatient clinic and all
patients were given a complete demonstration of how to apply
the topical glycopyrrolate and its possible complications.
Patients were warned to avoid touching their eyes, noses and
mouths before washing their hands after application of topical
glycopyrrolate. The study was approved by the Research Ethics
Committee and written informed consent was obtained from
each patient before the procedure.
Sweat production was measured by gravimetric assessment
in a seated position. The amount of sweat was quantified
using absorbent papers. At baseline, two absorbent square
papers (5 · 5 cm) per patient were prepared and weighed on
a high-precision laboratory scale (accuracy ± 0Æ1 mg; Sartorius
CP224S, Göttingen, Germany), and the weights were record-
ed. All measurements were processed by the same researcher
in the same room. Neutral environmental conditions of room
temperature (20–24 C) and relative humidity (40–60%)
were maintained during this study. Each patient’s forehead
was thoroughly cleansed and dried with gauze for 1–2 min
and divided into two parts (left and right) to compare sweat
production. The 2% topical glycopyrrolate pad (Fig. 1) was
folded in half and wet pads were lightly rubbed on one half
of the forehead of each patient while the other half served as
control with a placebo (saline) application. The order in dis-
tribution of left and right was randomized by a computer pro-
gram. After 90 min, a trigger that was significant to each
patient was provided until severe sweating mimicking that of
his ⁄her daily life was produced. Each patient chose his ⁄her
own trigger, such as the consumption of spicy food (hot pep-
pers or chips), walking up and down the stairs, applying
warm air to his or her body (Bair Hugger Warming Unit –
Model 505; Arizant Health Care Inc., Eden Prairie, MN,
U.S.A.), or being stared at to evoke an emotional disturbance.
Prepared papers were placed simultaneously on the two parts
of the forehead for 5 min and were then reweighed. The rate
of sweat production (in mg min)1) was then calculated over
5 min. The differences in weight between the prepared papers
and reweighed papers after treatment were taken as sweat
Fig 1. Drying pads (53 mm diameter) for applying 2% topical
glycopyrrolate or placebo (saline) and container used to prevent
evaporation.
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Journal Compilation  2008 British Association of Dermatologists • British Journal of Dermatology 2008 158, pp1094–1097
Topical glycopyrrolate for facial hyperhidrosis, W.O. Kim et al. 1095
production.7 Minor’s iodine–starch test was not performed
because of the clear visualization of sweat reduction on the
side where topical glycopyrrolate was applied.
We interviewed each of the patients after provocative trig-
gering and 1 week later in person during follow-up visits or
via the telephone. Patients were asked to complete a question-
naire evaluating the results of sweating, degree of satisfaction,
complications, and period of recurrence (the time required
for sweating to return to its original condition). The results of
sweat reduction on the 2% topical glycopyrrolate-treated fore-
head were graded by the patients as ‘excellent’ when the
patient did not detect any sweating, ‘good’ when the patient
had marked improvement with minimal sweating under
stressful conditions, ‘fair’ when the patient had marked
improvement but was aware of light sweating after the trig-
ger, or ‘poor’ when the patient had limited improvement and
was very aware of sweating. The degree of satisfaction of each
patient was evaluated as ‘satisfied’, ‘partially satisfied’ or ‘dis-
satisfied’. Complications and recurrence after treatment consti-
tuted the patient’s subjective observations and experiences just
after triggered provocation and 1 week later.
The differences in the absorbent paper weights between
baseline and after treatment using topical glycopyrrolate or
saline were calculated and statistical analyses were performed
using SPSS 10.0 for Windows (SPSS, Chicago, IL, U.S.A.). The
two-sided Wilcoxon signed rank test for paired samples was
used to compare the efficacy of reducing sweat production.
Results
Sweat production was measured by weighing absorbent papers
before and after treatment. No significant difference was seen
between the prepared papers before administration of topical
glycopyrrolate and placebo (P > 0Æ05). However, the sweat
production rate at the forehead treated with 2% topical glyco-
pyrrolate was significantly reduced at 37Æ6 ± 2Æ8 mg min)1
(mean ± SEM) compared with 102Æ2 ± 5Æ5 mg min)1 for the
placebo-treated forehead (P < 0Æ001), corresponding to a
reduction of 61Æ8 ± 3Æ2%. ‘Excellent’ was reported by six
patients (24%), 16 patients (64%) reported ‘good’, two
patients (8%) reported ‘fair’, and one patient (4%) reported
‘poor’. In general, patient satisfaction was fairly high. Most
patients reported a significant reduction in forehead sweating
after treatment with topical glycopyrrolate and wished to con-
tinue with the treatment except for one patient who experi-
enced a transient headache. Twenty patients were ‘satisfied’,
four patients were ‘partially satisfied’ because the amount of
sweat reduction was lower than their expectations, and one
patient was ‘dissatisfied’ because of a transient headache that
developed after treatment. Topical glycopyrrolate was well
accepted and tolerated in most patients, and apart from the
one patient with a mild headache that occurred in the evening
after treatment, no other side-effects or complications were
reported after 1 week. Despite the high acceptance of topical
glycopyrrolate, long-lasting side-effects were not observed.
Patients did not experience skin allergies or local reactions
1096 Topical glycopyrrolate for facial hyperhidrosis, W.O. Kim et al.
during the experimental session and remained completely free
of dermal side-effects. More serious complaints, such as
blurred vision, dry mouth, dizziness, or skin irritation, were
not reported. The period before recurrence was < 1 day in
seven patients (28%). Seventeen patients (68%) experienced
light sweating on their foreheads on the day of treatment and
returned to their original pattern of sweating after 2 days.
One patient (4%) had continued anhidrosis up to 4 days after
treatment.
Discussion
Craniofacial and gustatory hyperhidrosis is a facial form of
focal hyperhidrosis that has been overshadowed by palmar,
plantar and axillary hyperhidrosis.4,8,9 Craniofacial hyperhi-
drosis is a primary hyperhidrosis that tends to affect more
men than women and is triggered by emotional stimuli and
food much more frequently than hyperhidrosis at other sites.8
Gustatory hyperhidrosis in this study is a secondary hyperhi-
drosis following T2–3 sympathectomy, occurring in as many
as one-third of patients.10,11 When patients are confronted by
triggers such as spicy food, exercise, heat or emotional dis-
tress, excessive sweat may develop on their faces and cause
suffering.
Focal facial hyperhidrosis may be troublesome for patients
because it is associated with a negative quality of life. Various
conservative therapeutic modalities, such as topical application
of aluminium compounds and oral medication with anticho-
linergics or beta-blockers, have been prescribed.4,12,13 How-
ever, these options do not deliver the desired results for
patients. Endoscopic thoracic sympathectomy may be consid-
ered an effective treatment for craniofacial sweating. Although
some patients hope that surgery will provide long-term bene-
fits, the adverse effects, including compensatory sweating,
may cause patients to regret the procedure. Such adverse
events are currently unpredictable, and a surgical approach is
not a widely available option as first-line therapy.14 In con-
trast, intradermal injections of botulinum toxin have been
reported as an effective temporary treatment for focal facial
hyperhidrosis with a low risk of side-effects.7,15 Botulinum
toxin is a safe and effective treatment lasting at least 5 months.
The side-effects include pain at the site of injection, ptosis,
and partial disability in frowning of the forehead in half of
the patients.7 Moreover, it is not easily applicable to the whole
face due to the high cost, and can result in an asymmetrical
face or limited facial expressions.
Topical anticholinergics can be an alternative to botulinum
toxin and an attractive first-line treatment of facial
sweating.3–5,16 Anticholinergics have the ability to inactivate
sweat glands by the action of acetylcholine and may be more
attractive to patients than simply occluding sweat ducts with
aluminium compounds that can cause itching, stinging and
skin irritation. Oral anticholinergics such as glycopyrrolate and
oxybutynin have been used, but sometimes dry mouth can
result as a major problem, thereby leading to discontinuance.
Topical glycopyrrolate is practical and has few side-effects
Journal Compilation  2008 British Association of Dermatologists • British Journal of Dermatology 2008 158, pp1094–1097
compared with oral administration. On objective and subjec-
tive evaluation assessments, most patients were greatly relieved
after treatment with topical glycopyrrolate. Topical glyco-
pyrrolate application (2%) proved to be an effective, safe, and
satisfactory method of treatment for facial hyperhidrosis on
the forehead in our study. Sweat reduction was significant
according to a 5-min gravimetric assessment. Our gravimetri-
cally controlled study demonstrated that topical glycopyrrolate
was an effective treatment option for the control of focal facial
hyperhidrosis, with good short-term results confirmed by the
1-week data. Minor’s iodine–starch test, the most common
measuring method, was not conducted due to clear visualiza-
tion of sweat reduction, and although it might be useful for
recognizing sweat, the resulting amount cannot be quanti-
fied.12 Use of the 2% topical glycopyrrolate pad gave a signifi-
cant reduction of sweat production (61Æ8%, P < 0Æ001). Most
patients expressed satisfaction following random half-forehead
treatment with topical glycopyrrolate, and expressed their
desire to continue with the treatment. Only one patient,
who developed a transient headache after treatment, was dis-
satisfied.
Glycopyrrolate is a quaternary ammonium anticholinergic
agent that penetrates the skin slowly and does not cross the
blood-brain barrier. Therefore, when applied topically in pad
or cream form or by other methods such as dabbing on an
aqueous solution with the finger tips, it has been associated
with few adverse effects. However, topical use to avoid sys-
temic side-effects can result in contact sensitization and the
high concentration of drug needed for sufficient absorption
through the skin can affect cholinergic nerve endings that may
lead to systemic absorption and adverse effects.17 The side-
effects and complications included mild headache in one
patient but the other patients did not have any complaints.
The cause of the headache is not clear. Serious side-effects
were not seen in our patients. Although the duration of the
effect was limited to 1 or 2 days, its effects lasted at least
1 day.
In conclusion, 2% topical glycopyrrolate appears to be an
acceptable, safe, and effective treatment for forehead sweating
caused by provocative triggering in craniofacial and gustatory
hyperhidrosis. It may be applied on a daily basis or before
certain occasions, such as prior to social activities. Although
topical glycopyrrolate is convenient to use, the limitation is
that the effects lasted only 1 or 2 days in response to a single
application. Further study is needed for objective evaluation of
its safety and long-term results on the face.
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