Metformin’s anti-androgenic effect may explain its efficacy in the treatment of hirsutism, which results from elevated circulating androgens (testosterone, dihydrotestosterone (DHT), and androstenedione) in women with PCOS. The 5-alpha reductase type 2 isoenzyme concentrated in the outer root sheath of hair follicles predominantly in the beard and genital hair DHT causes terminalization of the vellus hair and prolongs the anagen phase resulting in longer thicker hair. Metformin reduces the amount of free testosterone available for conversion into DHT.
It is important to differentiate the pathophysiology of PCOSrelated hirsutism from idiopathic hirsutism before speculating the role that metformin plays. Mohammed et al’s study (n=85) comparing patients with PCOS-related, idiopathic, and idiopathic hirsutism discovered that there is a significant inverse correlation between testosterone and omentin-1, a biomarker speculated to be involved in the development of non-PCOS related hirsutism.
Tolerability and Adverse Effects of Metformin
Metformin is generally well-tolerated by most patients, with mild-to-moderate short-term gastrointestinal upset cited as the most common side effect, albeit no incidences of lactic acidosis or severe hypoglycemia were reported. There was one isolated case of anemia reported by Singh and Bhansali was considered l, and a few reported cases of hyperpigmentation speculated to be associated with the patients’ insulin resistance state.5 Metformin is rarely prescribed by dermatologists due to the prevailing notion that its use falls within the realm of primary providers or endocrinologists, as well as concerns regarding side effects. However, dermatologists should more frequently consider metformin as an adjunct therapy given its promising results combined with its good tolerability.
It is important to differentiate the pathophysiology of PCOSrelated hirsutism from idiopathic hirsutism before speculating the role that metformin plays. Mohammed et al’s study (n=85) comparing patients with PCOS-related, idiopathic, and idiopathic hirsutism discovered that there is a significant inverse correlation between testosterone and omentin-1, a biomarker speculated to be involved in the development of non-PCOS related hirsutism.
Tolerability and Adverse Effects of Metformin
Metformin is generally well-tolerated by most patients, with mild-to-moderate short-term gastrointestinal upset cited as the most common side effect, albeit no incidences of lactic acidosis or severe hypoglycemia were reported. There was one isolated case of anemia reported by Singh and Bhansali was considered l, and a few reported cases of hyperpigmentation speculated to be associated with the patients’ insulin resistance state.5 Metformin is rarely prescribed by dermatologists due to the prevailing notion that its use falls within the realm of primary providers or endocrinologists, as well as concerns regarding side effects. However, dermatologists should more frequently consider metformin as an adjunct therapy given its promising results combined with its good tolerability.
CONCLUSION
High-dose and long-term therapy (>6 months) ranging from
1,000–2,000mg metformin/day has demonstrated promising
efficacy in the treatment of psoriasis, HS and PCOS-related
acne. This efficacy may be attributed to the anti-inflammatory
effect of the drug at high systemic levels. Patients generally
tolerate metformin well, which should provide reassurance
for dermatologists to consider the addition of this adjunctive
therapy. The treatment of PCOS related AN and hirsutism may
require a more aggressive, and sustained course (>6 months)
of metformin treatment regimen (starting and maintenance
dose upwards of 1500mg). Metformin is safe and efficacious
to use as an adjunct to oral contraceptives, statins, vitamin D,
retinoids, and other first line treatments for psoriasis, HS, and
PCOS, however, should not be used in conjunction with other
insulin-lowering agents without close monitoring by endocrine
specialist. However, limited and mixed results warrant further
research regarding metformin’s application for acanthosis
nigricans and hirsutism to determine whether at higher doses may be more effective in patients with for both obese and nonobese
female patients with PCOS.
DISCLOSURES
The authors have received no financial funding for the research
and have no conflicts of interest to disclose.
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