CLINICALLY PROVEN

Clinical Studies

The HairDX Genetic Test for Female Androgen Sensitivity

Recent advances in human genetics empower researchers to discover the genetic basis of drug response to many common conditions. As genetic science is evolving at a rapid pace new discoveries are made almost daily.  Daniel Alain is committed to providing the latest in genetic discoveries to physicians and their patients. The new HairDX Genetic Test for Female Androgen Sensitivity helps physicians determine if your hair loss has an androgenic basis. Patients with high androgen sensitivity could benefit from anti-androgen therapies such as finasteride*, spironolactone, etc.

Finasteride is a synthetic anti-androgen (type II 5-α reductase inhibitor) used for treatment of androgenic disorders, such as male pattern hair loss (androgenetic alopecia - AGA). However, the efficacy of finasteride in the treatment of female AGA has been inconsistent. Previous, large-scale clinical studies using 1 mg/day finasteride failed to show efficacy among the study participants. However, subsequent smaller studies and case reports have shown a positive response occurs in some women (1). Importantly, none of these studies considered individual genetic variations as a possible factor in medication response. Recent studies evaluating variants in the androgen receptor (AR) gene in men revealed a positive association between the variant associated with increased androgen sensitivity and finasteride response to treat AGA (2-4). Androgen sensitivity on the AR gene is determined by repeat sequences of the amino acid glutamine which is formed from a sequence of three nucleotides, known as CAG, on the DNA backbone that makes up the gene. This variant is often referred to as the number of CAG repeats on the AR gene. Fewer CAG repeats are associated with increased androgen sensitivity (5). The AR gene is located on the X-chromosome, and women carry two X chromosomes in each cell; therefore, all women have two copies of the AR gene. That means that each gene has an opportunity to influence the androgen sensitivity of the cell. Within a single cell, only one AR gene copy is active, while the second AR gene copy is inactivated through the process of X-chromosome inactivation (XIA). By measuring the percentage activation of each AR gene copy, it is possible to weight the contribution to a patients androgen sensitivity. A patient with a shorter weighted average number of CAG repeats in their AR gene is more androgen sensitive. Based on previous published studies evaluating AR CAG repeats in women/girls, it is expected that patients with the androgen sensitive genotype are more likely to respond to anti-androgenic therapies when treating androgenic conditions like AGA.

A double-blind, placebo-controlled female finasteride response study conducted by Dr. Sharon Keene demonstrated that all women with an XIA-weighted AR CAG repeat length of <23.5 (n=6) had a positive response to 1 mg/day finasteride therapy for their AGA (6). In contrast, patients with an XIA-weighted AR CAG repeat length of ≥23.5 (n=2) displayed no response to finasteride therapy. Furthermore, all patients on the placebo (n=5) failed to show any improvement in hair growth. The results from this study have been replicated in an independent cohort.

The HairDX Genetic Test for Female Androgen Sensitivity provides a physician with their patient’s XIA-weighted** AR CAG repeat length and allows the physician to compare the results to the current scientific literature. In general, a shorter XIA-weighted AR CAG repeat length of (<23.5) is associated with greater androgen sensitivity and studies and case reports demonstrate a greater likelihood that a patient will experience a significant benefit by using an anti-androgenic therapy such as finasteride for the treatment of AGA (6). Furthermore, a previous study of anti-androgenic therapy in adolescents with preclinical ovarian androgen excess have demonstrated a similar relationship between AR CAG repeat lengths and treatment response (7).

*At this time certain anti-androgen therapies such as finasteride are not approved by the U.S. FDA for use in women. This test does not endorse or encourage the use of off-label prescription medication.

** The HairDX Genetic Test for Female Androgen Sensitivity normally determines the X-chromosome inactivation via epigenetic analysis; however, in some cases the results are determined by inference due to patient allele distribution.

References

• Camacho-Martínez FM. Hair loss in women. Semin Cutan Med Surg. 2009;28:19-32.
• Sato A, et al. Correlation between polymorphic CAG-repeats in the androgen receptor gene and therapeutic efficiency of finasteride in androgenetic alopecia. Skin Surgery. 2008;17(2):80-6.
• Sato A, et al. Polymorphic CAG repeats in androgen receptor gene and their implication in androgenetic alopecia. Skin Surgery: 2006;15(2):67-74.
• Wakisaka N, et al. Effectiveness of finasteride on patients with male pattern baldness who have different androgen receptor gene polymorphism. J Investig Dermatol Symp Proc. 2005;10:293-4.
• Palazzolo I, et al. The role of the polyglutamine tract in the androgen receptor. J Steroid Biochem Mol Biol. 2008;108:245-53.
• Keene SA, et al. Epigenetic markers predict treatment response to finasteride in female androgenetic alopecia. 6th Congress for Hair Research - Poster. 2010 June, Cairns, Australia.
• Ong KK, et al. Flutamide-metformin for post-menarcheal girls with preclinical ovarian androgen excess: evidence for differential response by androgen receptor genotype. Eur J Endocrinol. 2007;157:661-8.