INTRODUCTION
Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease of the apocrine gland-bearing areas such as the axilla, groin, and perianal skin, which is characterized by deep seated painful nodules, abscesses, and sinus tracts, eventually resulting in cicatricial scars.1 Lesions may extend to the buttocks, thighs, chest, scalp, eyelids, and retroauricular areas.2 The worldwide prevalence is around 1% and most commonly occurs in adolescents after the onset of puberty.3 Pre-pubertal children comprise 2% of the cases.4 The disease often progresses into adulthood and is associated with a grave psychological burden.
Role of Androgens in the Pathogenesis of Hidradenitis Suppurativa
A variety of factors, including the occurrence of disease after the onset of puberty, suggest the role of hormones in the pathogenesis of HS. Women have a 3 times higher prevalence of HS than men and occasionally suffer from premenstrual flares, usually at the time when estrogen levels are low.5,6 Premenstrual flares occur in the luteal phase of the cycle when there is an ovarian androgen boost, suggesting a possible role of androgens in HS.7 HS in post-menopausal women has only rarely been reported.6,7 Reduction in disease activity can occur during pregnancy when the progesterone levels are high, followed by rebound flares in the immediate postpartum period.8
Although preliminary studies showed raised plasma testosterone levels in females with HS,9 further studies found no significant difference in the serum androgen levels between HS patients and controls.10 This led to the speculation that the probable cause for androgenic overactivity was end organ receptor hypersensitivity to normal levels of circulatory androgens.11,12 There were no significant differences in the estrogen and androgen receptors in the apocrine gland cells in a study conducted on 22 patients.13 However, raised receptor count is no prerequisite for increased end organ sensitivity, as it can occur as an intrinsic property of the receptor through post-transcriptional or post-translational protein modification.14,15
Recent studies suggest occlusion of the pilosebaceous unit to be the key initiator in HS pathogenesis.3,16 The exact pathomechanism is unknown, but alterations in the sebaceous gland physiology may also play a role. Kamp et al demonstrated reduction in the density of sebaceous glands in HS patients.17 Reduction in sebocytes may lead to deficient production of lipids and antimicrobial peptides, which may allow persistence of cutaneous bacterial flora and exaggerated inflammatory response. Also, reduction in sebum may increase hair follicle fragility, causing it to rupture and subsequently perpetuate inflammation of the surrounding skin.17
Role of Androgens in the Pathogenesis of Hidradenitis Suppurativa
A variety of factors, including the occurrence of disease after the onset of puberty, suggest the role of hormones in the pathogenesis of HS. Women have a 3 times higher prevalence of HS than men and occasionally suffer from premenstrual flares, usually at the time when estrogen levels are low.5,6 Premenstrual flares occur in the luteal phase of the cycle when there is an ovarian androgen boost, suggesting a possible role of androgens in HS.7 HS in post-menopausal women has only rarely been reported.6,7 Reduction in disease activity can occur during pregnancy when the progesterone levels are high, followed by rebound flares in the immediate postpartum period.8
Although preliminary studies showed raised plasma testosterone levels in females with HS,9 further studies found no significant difference in the serum androgen levels between HS patients and controls.10 This led to the speculation that the probable cause for androgenic overactivity was end organ receptor hypersensitivity to normal levels of circulatory androgens.11,12 There were no significant differences in the estrogen and androgen receptors in the apocrine gland cells in a study conducted on 22 patients.13 However, raised receptor count is no prerequisite for increased end organ sensitivity, as it can occur as an intrinsic property of the receptor through post-transcriptional or post-translational protein modification.14,15
Recent studies suggest occlusion of the pilosebaceous unit to be the key initiator in HS pathogenesis.3,16 The exact pathomechanism is unknown, but alterations in the sebaceous gland physiology may also play a role. Kamp et al demonstrated reduction in the density of sebaceous glands in HS patients.17 Reduction in sebocytes may lead to deficient production of lipids and antimicrobial peptides, which may allow persistence of cutaneous bacterial flora and exaggerated inflammatory response. Also, reduction in sebum may increase hair follicle fragility, causing it to rupture and subsequently perpetuate inflammation of the surrounding skin.17
Sebaceous glands are capable of producing cholesterol from acetate de-novo and are also capable of production of glucocorticosteroids and sex hormones.18-21 Sebocytes occasionally express 3β-hydroxysteroid dehydrogenase 1 enzyme, responsible for the catalyzation of dihydroxy epiandrostenidione (DHEA) to androstenedione, initiating the synthesis of testosterone in situ. Also, peripheral conversion of circulatory dihydroxy epiandrostenidione sulfate (DHEAS) to DHEA by the enzyme steroid sulfatase may take place in the sebaceous gland and the terminal hair follicle.22 The 5α-reductase type 1 enzyme responsible for conversion of testosterone to more potent dihydro-testosterone is also seen predominantly in the skin.23,24
HS is also known to be associated with metabolic syndrome, ie, central obesity, diabetes mellitus, hypertension, high triglycerides, and low high density lipoproteins.25 A meta-analysis of 3950 patients with HS showed a prevalence of metabolic syndrome in 9.64% patients, and there was also a significant association of HS with metabolic syndrome in the pediatric population.1 Metabolic syndrome was found to be present in 40% of the cases compared with 13% in controls in a hospital-based case control study26; and a cross-sectional study comprising 3207 patients also supported this association.27 Since elevated insulin and insulin-like growth factors are indirectly linked to increased sensitivity of circulatory androgens to androgen receptors, HS may be aggravated in patients with metabolic syndrome. Moreover, obesity is associated with low serum levels of sex hormone-binding globulin (SHBG), leading to raised circulatory androgens.28,29 These factors support the use of antiandrogens in treating HS. In this review, a brief outlook on the use of hormonal treatment is presented as a narrative.
HS is also known to be associated with metabolic syndrome, ie, central obesity, diabetes mellitus, hypertension, high triglycerides, and low high density lipoproteins.25 A meta-analysis of 3950 patients with HS showed a prevalence of metabolic syndrome in 9.64% patients, and there was also a significant association of HS with metabolic syndrome in the pediatric population.1 Metabolic syndrome was found to be present in 40% of the cases compared with 13% in controls in a hospital-based case control study26; and a cross-sectional study comprising 3207 patients also supported this association.27 Since elevated insulin and insulin-like growth factors are indirectly linked to increased sensitivity of circulatory androgens to androgen receptors, HS may be aggravated in patients with metabolic syndrome. Moreover, obesity is associated with low serum levels of sex hormone-binding globulin (SHBG), leading to raised circulatory androgens.28,29 These factors support the use of antiandrogens in treating HS. In this review, a brief outlook on the use of hormonal treatment is presented as a narrative.
MATERIALS AND METHODS
A detailed search was conducted on databases such as Pubmed, EMBASE, Google Scholar, and Cochrane Central using key words like "hidradenitis suppurativa", "acne inversa", "antiandrogens", "hormonal therapy", "hidradenitis suppurativa and antiandrogens", "hidradenitis suppurativa and spironolactone", "hidradenitis suppurativa and cyproterone acetate", and "hidradenitis suppurativa and OCPs". After initial screening, relevant studies including case series, retrospective and prospective uncontrolled and controlled studies in English literature were reviewed in depth and the report was prepared.
Hormonal Therapy in Hidradenitis Suppurativa
Finasteride
Finasteride is a competitive inhibitor of type II 5α-reductase
with no effect on the type 1 isoenzyme, unlike dutasteride. Finasteride is effective in blocking the conversion of testosterone
to dihydrotestosterone (DHT) by the 5α-reductase enzyme and thereby altering the receptor sensitivity at the terminal hair follicle.30 Its use in androgenic alopecia and hirsutism has already been established.31 In HS, the evidence in support of finasteride is based on case reports and case series.
In HS, the role of anti-androgenic action of finasteride was demonstrated by Joseph et al in a small case series of 7 patients. Two male and 5 female patients with HS were treated with finasteride 5 mg QD dose for a duration varying from 6 to 16 weeks. Lesions healed in 3 patients, the rest experienced a reduction in the number inflammatory lesions, and no new lesions were seen during the course of treatment. Recurrence was seen in 3 patients after stopping the drug but was controlled by retreatment with finasteride. Response to treatment could be noticed as early as week 2, while in some cases a response took 12 weeks of continuous treatment. Remission lasted for 8 to 18 months.12
Finasteride has also been tried in children aged between 6 and 11 years in a series by Mota et al. No child suffered from hormonal abnormalities at the time of treatment. Finasteride was initiated at 1 mg and gradually increased to 5 mg in the event of inadequate response. The only male child in the series was started with finasteride at a dose of 1 mg. The treatment lasted 24 weeks except in one case where it was stopped at week 12 at a parent’s request. An overall improvement in the number of inflammatory lesions was seen, and there was a reduction in the frequency and intensity of HS flares. No new lesions occurred during the treatment. Remissions lasted for 6 to 24 months. No side effects were observed during the course of treatment in any patient.32
In another case series by Randhawa et al, 3 female children with HS were treated with finasteride 5 mg to 10 mg QD dose for a duration varying from 3 to 6 years. Significant improvement was seen in the severity of lesions and number of flares.33 Similar results were obtained when a 28-year-old male patient with HS on the face was treated with finasteride 5 mg QD for 1 year. The lesions healed completely with residual scarring.34
Treatment with finasteride in the early stages of disease is more beneficial as it can reduce morbidity to a great extent.31 With the limited data available it is difficult to ascertain the duration of treatment required for complete remission of the disease. In most cases, response to treatment was seen after a latency of 2 to 4 weeks.31
Finasteride is metabolized by the cytochrome P (CYP) enzymes in the liver and excreted by the liver and kidney. Renal disorder dose adjustments are not required.30
