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Review of Second Line Therapy Options for Hyperhidrosis: Topical Glycopyrrolate, Microwave Therapy, and Botulinum Toxin

Ariana Eginli, MD

Hyperhidrosis, or excessive sweating, is a fairly common disorder that affects nearly 5% of the world’s population and frequently is associated with a diminished quality of life. In fact, patients with hyperhidrosis report a worse quality of life compared to patients with atopic dermatitis or psoriasis.1

Typical treatment options for hyperhidrosis include topical aluminum chloride or anticholinergic drugs, oral medications, iontophoresis, botulinum toxin, sympathetic nerve block using alcohol, or sympathectomy.  Selection of appropriate therapy for hyperhidrosis depends on several factors including consideration of location of involvement (axillary, palmar, plantar, or craniofacial), disease severity, cost, treatment availability, and safety concerns.

First-line therapy often begins with topical medications such as aluminum chloride.  Topical glycopyrronium (or glycopyrrolate) is a relatively newer treatment option for patients with hyperhidrosis, and is considered a second-line therapy option. It is an anticholinergic drug that inhibits the action of acetylcholine on sweat glands, thus reducing sweating.  As of now, once daily use of topical glycopyrronium 2.4% in the form of impregnated towelettes is FDA approved for treating axillary hyperhidrosis; but its safety and minimal side effects (compared to oral glycopyrrolate) make it a plausible option for treating hyperhidrosis in other anatomical locations.

In a double-blinded, placebo-controlled, split-face study, 39 participants with facial hyperhidrosis were treated with 2% glycopyrrolate that was impregnated in cotton pads on one-half of the forehead, whereas the other half of the forehead was treated with a placebo, once a day for 9 successive days.2  Total sweat weight and the Hyperhidrosis Disease Severity Scale (HDSS) score were evaluated at baseline, 90 minutes after the first application (day 1), 24 hours after the first application (day 2), and 24 hours after eight additional successive daily applications (day 10).  The glycopyrrolate-treated sides showed a reduction in the rate of sweat production at the forehead of 25.16 ± 10.30% on day 1, 29.63 ± 7.74% on day 2, and 36.68 ± 11.41% on day 10. The topical glycopyrrolate-treated half of the forehead had a slight, but not statistically significant, decrease in HDSS score. Only one patient reports transient headaches after treatment, but otherwise no other adverse effects were reported. Common concerning side effects from topical glycopyrrolate include mydriasis, dry nose, and dry throat, but these were avoided by having patient’s wash their hands after application and avoid touching their eyes, nose, and mouths.  The authors conclude that topical glycopyrrolate is a safe and effective option for treating facial hyperhidrosis.2  

Other second-line therapy options include microwave thermolysis and botulinum toxin. Microwave energy can be utilized to destroy eccrine glands.  Glaser et al3 conducted a randomized, sham-controlled, blinded study with 120 adults with primary axillary hyperhidrosis, who were given one to three treatments with a microwave energy device (n=81) or a shave device (n=39).  The patients treated with the microwave device were more likely to report a reduction in sweat severity after 30 days of treatment than patients in the sham treated group (89% versus 54%).  A statistically significant difference occurred for all follow-up visits through 6 months, and the active group showed stable efficacy through their final follow-up visit on the 12th month.  Using gravimetric assessment of sweat production, the authors were able to show a 50% or more reduction in the sweat at the 30-day follow-up visit in 80% of the active group and 67% of the sham group.  When success was defined as 75% or greater reduction in sweat, there was a statistically significant difference between the two groups (62% of the active group vs 39% of the sham group).  However, at later time points, there was no statistically significant difference between the two groups, though the active group continued to have lower gravimetrically measured levels of sweat.3

Botulinum toxin can help treat hyperhidrosis by blocking the release of acetylcholine from the presynaptic junction of both neuromuscular and cholinergic autonomic neurons.  In a 16 week multicenter randomized control trial involving 320 participants with bilateral primary axillary hyperhidrosis, response rates after 4 weeks were significantly higher with botulinum toxin type A (Botox), 50 units per axilla by 10-15 intradermal injections, than placebo.4  Overall, 94% (227) of the Botox group had responded (defined as a ≥50% reduction from baseline of spontaneous axillary sweat production) versus 36% (28) of the placebo group, and 82% versus 21%, respectively, by week 16.  Also, participants in the Botox group reported significantly higher patient satisfaction compared to the placebo group.  The authors concluded that Botox is a safe and effective treatment option for primary axillary hyperhidrosis with high levels of patient satisfaction.


  1. Naumman M, Hamm H, Spalding JR, Kowalski J, Lee J. Comparing the quality of life effects of primary focal hyperhidrosis to other dermatological conditions as assessed by the dermatology life quality index (DLQI). Value Health. 2003;6(3):242. doi:10.1016/S1098-3015(10)63957-5
  2.  Hyun MY, Son IP, Lee, Y, et al.  Efficacy and safety of topical glycopyrrolate in patients with facial hyperhidrosis: a randomized, multicenter, double-blinded, placebo-controlled, split-face study. J Eur Acad Dermatol Venereol. 2015;29(2):278. doi:10.1111/JDV.12518
  3. Glaser DA, Coleman WP III, Fan LK, et al. A randomized, blinded clinical evaluation of a novel microwave device for treating axillary hyperhidrosis: the dermatologic reduction in underarm perspiration study. Dermatol Surg. 2012;38(2):185. doi:10.1111/j.1524-4725.2011.02250.x
  4. Naumann M, Lowe NJ. Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomized, parallel group, double blind, placebo controlled trial. BMJ. 2011:323(7313):596. doi:10.1136/bmj.323.7313.596.




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