Polymorphisms of the Androgen Receptor Gene and Hormonal Contraceptive Induced Provoked Vestibulodynia

Abstract

Aim Women who developed vestibulodynia (vulvar vestibulitis) while taking combined hormonal contraceptives (CHCs) and a control group of women were tested for polymorphisms of the gene coding for the androgen receptor (AR) that is located on the X chromosome. Study Design DNA from 30 women who developed vestibulodynia while taking CHCs and 17 control women were tested for the number of cytosine–adenine–guanine (CAG) trinucleotide repeats in the AR. In addition, serum-free testosterone was tested in both groups. Results The mean number of CAG repeats in the study group was significantly greater than the control group (22.05±2.98 vs. 20.61±2.19, respectively; P =0.025). This significant difference persisted when analyzing the CAG repeats from the longer allele from each subject. Among those who were taking drospirenone-containing CHCs, the mean calculated free testosterone was 0.189±0.115ng/dL in the study group and 0.127±0.054ng/dL in the control group, all of whom were taking drospirenone-containing CHCs (P =0.042). Conclusion In the study cohort, women who developed vestibulodynia while taking CHCs are more likely to have longer CAG repeats in the AR than women who took the same type of CHC but did not develop vestibulodynia. We speculate that the risk of developing CHC-induced vestibulodynia may be due to lowered free testosterone combined with an inefficient AR that predisposes women to vestibular pain.

Female Sexual Pain Disorders: a Review of the Literature on Etiology and Treatment

“…Working with physical therapists, Reissing et al [50] found that women with vaginismus demonstrated significantly higher vaginal/pelvic muscle tone and lower muscle strength than women with PVD or controls. Single Bcandidate^gene research has been performed in the field of vulvodynia, and genetic polymorphisms have been linked to the development of vulvar pain [51][52][53][54][55][56]. Although to date, there is evidence for heritability in other chronic pain syndromes [57], no heritability studies have been performed in the context of vulvodynia.…”

Recent advances in understanding provoked vestibulodynia

“…Goldstein et al . 69 identified a genetic polymorphism in the AR in PVD patients and concluded that an inefficient AR combined with lowered free testosterone predisposes to PVD. This has not been confirmed.…”

Effect of local estrogen therapy (LET) on urinary and sexual symptoms in premenopausal women with interstitial cystitis/bladder pain syndrome (IC/BPS)

“…On the other hand, the local absorption of estrogen may influence the urinary environment exerting a protective action very similar to that observed in postmenopausal women [11]. Burrows and Goldstein have recently proposed the use of topical estradiol 0.03% and testosterone 0.01% to the vestibule twice daily in order to treat vestibulodynia in premenopausal women assuming CHC [31], a side-effect probably derived by a genetic disposition to have inefficient androgen receptor [32]. Interestingly enough, in our study sample, the rate of current or previous use of CHC is quite high suggesting the potential involvement of estro-progestin preparations in the pathophysiology of IC/PBS and/or the clinical expression of urinary/bladder and sexual symptoms associated with such condition.…”