Unconventional Methods of Epilation

This articles compiles some past research into (mostly pharmacological) methods of hair removal. IPL/photoepilation and electrolysis are not discussed here (and hopefully will be in a future article). Depilatory creams (e.g. those containing thioglycolic acid) are also not discussed since abundant information on those can be found elsewhere.

Pharmacological Interventions

TRPV

TRP channels (transient receptor potential cation channels) are a large group of ion channels consisting of six protein families, all sharing a similar structure and function, located mostly on the plasma membrane of numerous human cell types. One of these is the vanilloid family, TRPV. TRPV1 contributes to heat and inflammation sensations and mediates the pungent odour and pain sensations associated with capsaicin and piperine (i.e. the spicy sensation caused by chillies and peppercorns, respectively).

A study1 found that ‘capsaicin significantly inhibited hair shaft elongation in a time- and dose-dependent manner’ and concluded ‘taken together, the current study not only gives a hot new twist to human hair growth control by introducing TRPV1 signaling as a potent, physiologically relevant hair growth-inhibitory force that may be clinically exploited, eg, for the treatment of unwanted hair growth (hirsutism) by the topical application of TRPV1 agonists, and of hair loss (effluvium, alopecia) by administering TRPV1 antagonists.’ Another study2 found that ‘observations strongly suggested that combined administration of capsaicin and isoflavone might increase IGF-I production in hair follicles in the skin, thereby promoting hair growth.’

Activation of TRPV3 inhibits human hair growth in vitro3, thus ‘TRPV3 and the related intracellular signalling mechanism might function as a promising target for pharmacological manipulations of clinically relevant hair growth disorders’. In this paper, plant-derived agents, such as eugenol, thymol, and carvacrol - major components of clove, thyme, and oregano - and the synthetic agonist 2-aminoethoxydiphenyl borate (2-APB) significantly inhibited hair shaft elongation in a time- and dose-dependent manner.

TRPV4 is also expressed in human hair follicles and inhibits hair growth In vitro4, ‘cultures of human HF treated with GSK1016790A resulted in significantly decreased hair shaft elongation’.

Androgen receptor

As discussed previously, terminal hair (the dark thick hair formed by exposure to androgens) only somewhat regresses back to the vellus phase (small thin baby hair) even in complete absence of androgens. Hirsutism is treated by antiandrogens and 5-alpha reductase inhibitors to eliminate the underlying cause of hair growth, but this alone is generally insufficient to remove such hair5. However…

Topically applied glycyrrhizic acid (found in high concentrations in liquorice root and extract) causes hair removal in rats6. This study was conducted after “Anecdotic reports from Turkmenistan suggest an epilatory effect of sweet licorice extract after topical application”. Results showed that ‘after 3 d, 20–30% of the treated areas were free of hair. After treatment for 6–12 d, 90–95% of the hair was gone. Clinical as well as immunohistological examinations showed no signs of inflammation even after long-term treatment for more than 9 months. Interestingly, long-term treatment reduced the regrowth of hair of about 20%. Examination by scanning electron microscopy showed a smoothed hair cuticle that might facilitate detachment of the hair shaft from the follicular wall’. Liquorice has a known anti-androgenic effect and inhibits alpha five reductase and androgen receptors7.

Cyperus rotundus oil was found to be an effective and safe method to decrease hair growth89. ‘Eligible participants (n = 65) with unwanted axillary hair were assigned randomly to 1 of 3 study groups: topical C rotundus oil (group 1), saline (group 2), and Alexandrite laser (group 3). Sixty patients completed the entire study. Three methods were used to evaluate the results: hair counts, observations of independent professionals, and patient self-assessments. Overall results did not differ significantly between C rotundus oil and the Alexandrite laser (P > .05). However, statistically significant differences were noted with respect to decreased growth of white hair (P < .05), favoring the oil. This finding was evident by all 3 methods of assessment. No side effects were detected.’ (WTF!?)

Multiple recent anecdotal reports on reddit10 1112also seem to indicate that this treatment works well. The effect is attributable to the antiandrogenic activity of the oil. Almost seems too good to be true… Bobsincognito on reddit notes:

Same author and the same single picture as example. I saw the other published studies but they are plagiarized from the first. The study does seem to be comprehensive enough to believe. But why the others copied it? Only angle I can think of is to sell this expensive 'Rotundus' oil which seems to only be sourced from a single company in Egypt. Unless they sold a lot of this back when the study or story came out it's hard to see a huge profit.

Furthermore, a different study concluded that topically applied Cyperus rotundus oil increased hair growth in mice13. I remain skeptical… if this oil does indeed cause hair removal via androgen receptor antagonism, I don’t see why not use a better, more effective, synthetic topical anti-androgen instead.

Zinc sulphate and azealic acid were both found to potently inhibit 5-alpha reductase after topical application on human skin14. I have discussed other topical androgen receptor antagonists extensively in my androgenic alopecia article. Might also be worth looking into PROTACs15, for example ARV-110 which selectively degrades the androgen receptor and has had trials in humans16, seeing if they can be applied locally via transdermal absorption etc.

Could our good old trusty cyproterone acetate be applied topically? One study17 concluded that ‘the therapeutic effect of topically applied cyproterone acetate for acne treatment was clearly demonstrated. Topically applied sexual steroids in combination with liposomes are as effective as oral antiandrogen medication in acne treatment, while reducing the risk of adverse effects and avoiding high serum cyproterone acetate concentrations’ and another18, ‘we suggest the use of cyproterone acetate alcohol lotion as one of the main treatments for mild-moderate acne in female patients and as an adjuvant treatment for moderate to severe acne vulgaris’. Another older study19 noted the following results:

We have applied cyproterone acetate, as a 0.2% ethanolic solution, to a balding area of scalp skin of ten healthy male volunteers aged 24-55 for 8 months. The dose was 2 mg cyproterone acetate per day with a maximum of five applications per week, subject to the availability of the volunteers. Sebum excretion was estimated using our own modification of Schaefer’s ground-glass slide measuring technique.10 The sebuin-excretion rate fell considerably during the period of topical application of cyproterone acetate. After 14 weeks antiandrogen treatment the reduction in the sebum-excretion rate fell by between 48 and 68% in nine of the ten volunteers and by 25% in the tenth subject. The mean reduction was 56%. At the end of the 35-week application period, the mean reduction in sebum-excretion rate was 53% (36% and 45% in two subjects, 51-62% in the other eight).

So it probably does work? Given all the above, it might be worth trying topical cyproterone acetate formulation for hair reduction.

Other

Topically applied nicotinamide inhibited human hair follicle growth ex vivo and promoted catagen20. Despite this, another report demonstrated that topical niacinamide did not stimulate hair growth, and a further study showed that niacinamide could prevent premature catagen entry by inhibiting the expression of DKK-1 and protecting hDPCs against oxidative stress21. If nothing else, this serves as an important reminder that we need to be cautious about interpreting results from ex-vivo cell culture studies.

The timeless 1940’s classic, Applied Pharmacology by Clark22, gives us insight on some of the dark arts of depilation…

Thallium acetate, coal tar and X-rays, lovely.

Eflornithine (brand name Vaniqa) is an ornithine decarboxylase inhibitor (an enzyme that catalyses the rate-limiting step for follicular polyamine synthesis, which is necessary for hair growth) that decreases hair density and rate of growth. 81% percent of women showed clinical improvement after twelve months of treatment in clinical trials23. However, discontinuation of the cream caused regrowth of hair back to baseline levels within 8 weeks24. The cream works somewhat but can be quite expensive.

Insulin, IGF-1 and IGF-2 are all known promote hair growth25. Insulin sensitising agents (such as metformin, rosiglitazone and pioglitazone) lower elevated sugar levels in diabetics, and when given to nondiabetic subjects they only lower insulin levels (blood sugar levels will not change). Insulin-sensitising agents improve insulin action by increasing insulin sensitivity, thereby decreasing hyperinsulinemia. By reducing insulin levels they may also cause a reduction in circulating free androgens. The findings26 are summarised as follows:

In a recent randomized clinical trial, 40 women with PCOS and an impaired glucose tolerance test (IGT) were randomly assigned to 8 months treatment with rosiglitazone at either 2 or 4 mg/day (40). The majority of women in each group achieved improvements in hirsutism with lowering of total and free testosterone and endogenous ovulatory function, normal glucose tolerance and ovulatory menses at the end of the study period, with the degree of improvement being superior in the 4 mg rosiglitazone group compared with the 2 mg rosiglitazone group.

Another recent randomized clinical trial compared the effects of metformin (850 mg twice daily) and rosiglitazone (4 mg/day) on hirsutism in 96 patients with PCOS (41). After 24 weeks of treatment, patients’ F-G scores decreased in both treatment groups. However, a significantly greater reduction in scores was reported in the rosiglitazone group. This study found rosiglitazone to be more effective than metformin in the treatment of hirsutism.

An open-label study assessed the effects of rosiglitazone (4 mg/day) versus ethinyl estradiol 35 µg/cyproterone acetate (EE/CPA) 2 mg followed by their sequential combinations in 28 overweight women with PCOS (42). Rosiglitazone reduced insulin levels but had limited effects on hirsutism. EE/CPA was not found to modify insulin but led to a statistically significant increase in highdensity lipoprotein C and apolipoprotein A (p = 0.01) and a decrease in androgens and the degree of hirsutism. Similar changes occurred during combined treatments.

A small trial was carried out to assess the effects of 500 to 1500 mg metformin on hair growth (43). Sixteen women with PCOS and hirsutism were enrolled into a 14-month double-blind, placebocontrolled crossover study. Throughout the study, the severity of hirsutism was assessed using the F-G score, patient self-assessment, and growth velocity. Metformin treatment led to significant improvement in the F-G score and patient selfassessment. Growth velocity in millimeters per day at the end of each phase was also improved. The authors concluded that metformin treatment in this patient group led to a clinically and statistically significant improvement in hair growth compared with placebo.

A randomized clinical trial with hirsutism as the primary end-point compared the efficacy of metformin with combined ethinyl estradiol and cyproterone acetate (44). Patients with PCOS (n = 52) received either metformin (500 mg, three times daily) or Diane® 35/Dianette® for 12 months. Both objective and subjective methods of evaluating hirsutism were used as well as patients’ self-assessment scores. Metformin treatment resulted in greater improvements in the F-G score and patient self-assessment scores. Both treatments were moderately effective in reducing the hair diameter at multiple anatomical sites. The data suggest that hirsutism may be effectively treated by reducing hyperinsulinemia.

Other trials show metformin to result in small but significant improvement in hirsutism (45,46) or to have no effect (28). In an open-label study comparing the efficacy of metformin 1000 mg/day to 50 mg/day spironolactone in 82 women with PCOS, both treatments significantly improved hirsutism scores but spironolactone was more effective at slowing hair growth (22).

Despite all this, one very comprehensive meta-analysis27 found the following results:

Data synthesis: Of 348 candidate studies, 16 trials (22 comparisons) were eligible. The methodological quality of these trials was low. Random-effects metaanalyses showed a small decrease in Ferriman-Gallwey scores in women treated with insulin sensitizers compared with placebo [pooled weighted mean difference (WMD) of -1.5; 95% confidence interval (CI), -2.8 to -0.2; inconsistency (I(2)) = 75%]. There was no significant difference between insulin sensitizers and oral contraceptives (WMD of -0.5; CI, -5.0, 3.9; I(2) = 79%). Metformin was inferior to both spironolactone (WMD of 1.3; CI, 0.03, 2.6) and flutamide (WMD of 5.0; CI, 3.0, 7.0; I(2) = 0%).

Conclusions: Imprecise and inconsistent evidence of low to very low quality suggests that insulin sensitizers provide limited or no important benefit for women with hirsutism.

One article has suggested topical metformin as a potential option28.

Non-Pharmacological Interventions

Trichiasis is the ingrowth or introversion of the eyelashes, for which X-ray epilation has been used29. Following a total dose of 4,000 rad; ‘excellent results were achieved’, with the paper concluding that ‘x-ray therapy is an easy, safe, and painless method for the management and cure of chronic trichiasis’. In another case30 a man had a thick beard within his oral cavity due to a surgical defect which was treated with 50 Gy of X-ray radiation in 25 fractions. ‘At follow-up 1 month after completion of radiation, there was almost complete alopecia of the graft. The patient felt as though his taste had almost returned to normal and he denied any significant dryness. The radiation mucositis and dermatitis had resolved.’ They concluded ‘we are not advocating IMRT as a routine alternative to epilation, but an option in rare cases where epilation is not feasible and the potential benefits [...] outweigh the risks.’ X-ray epilation is further discussed on the informative article over at HairFacts31.

Many more strange approaches have been attempted over the years, mostly met with failure, or at least inconsistent results. These have included microwaves3233, photodynamic therapy34, electric tweezers, radio-frequency radiation35, ultrasound363738 and a whole myriad of other gadgets and gizmos. The history of these has been excellently documented on Andrea James’ website www.hairfacts.com as well as the associated forum hairtell.com/forum/. Also I highly recommend the book “Plucked: A History of Hair Removal”39 by Rebecca Herzig.

Notes