Acne is a skin condition caused by excessive sebum secretion, which piles up inside the hair follicles to form open and closed comedones, also called blackheads and whiteheads, respectively. Mild, moderate and severe forms of acne are usually distinguished clinically.
The condition is most common in adolescence and early adulthood, albeit can occur well into the forties. It has been postulated to be affected by the levels of sex hormones; however, this in turn may only be a symptom of a deeper anomaly.
Man with problematic skin and scars from acne. Image Credit: frank60 / Shutterstock
In keeping with this, the following indicators have been found to be associated with acne in males:
- A higher body mass index (BMI) and waist-hip ratio (WHR) which correlate with greater body fat
- Higher levels of blood pressure, both systolic and diastolic
- Higher basal glucose concentrations
- Higher insulin levels when challenged with an oral glucose tolerance test (OGTT)
Insulin Resistance and Acne
In some patients with acne there is the existence of a metabolic derangement which revolves around the presence of insulin resistance. Treating insulin resistance would, therefore, be a key target in preventing acne exacerbations in young males.
Reducing the glycemic load in food has been suggested and proved in many patients to be helpful in decreasing the incidence of acne. This may be because of the following factors:
- Increased glycemic load increases the insulin requirement, is associated with hyperphagia (i.e. extreme drive to consume food) and obesity, as well as increased levels of free fatty acids in the blood
- Insulin production may cause increased androgen secretion and potentiate androgenic effects by inducing the enzymes in steroidogenic pathways, and by stimulating the secretion of gonadotropin-releasing hormone and increased sex hormone binding globulin
- Insulin decreases the level of insulin-like growth factor 1 (IGF-1) binding protein, leading to increased activity of IGF-1 which stimulates cell proliferation
These effects of insulin produce the following changes:
- Basal keratinocytes within the duct of the hair follicle proliferate
- Superficial keratinocytes in the follicle are shed excessively
- Increased androgen activity stimulates sebum secretion
- The blocked follicle is colonized by Propionibacterium acnes with resulting inflammation
This is further supported by the well-known finding that females with polycystic ovarian syndrome (PCOS) have a higher prevalence of acne. The earliest metabolic disturbance here is insulin resistance, and it is associated with hyperinsulinemia and high androgen levels, with high IGF-1 and low sex hormone-binding globulin (SHBG) levels. When oral hypoglycemic agents are used to treat PCOS, it helps increase tissue sensitivity to insulin and thereby reduces acne.
Low-Glycemic Diet in Acne
Research has also shown that introducing a low-glycemic load diet improves insulin sensitivity, and accelerates weight loss (and lowers the BMI) despite adequate protein intake and low-glycemic index. The fact is that foods with a low glycemic index cause eaters to feel less hungry and experience fullness more rapidly, thus lowering the overall energy intake.
The association with BMI may apply only to males in the bracket of 18-25 years, based on several studies. Again, the altered nutritional profile of a low-glycemic diet may contribute to the improvement in acne, as for instance, better zinc and vitamin A intake.
Other Hormones in Acne
Assessing the levels of testosterone, as well as other androgenic hormones, as well as the sex hormone binding globulin, showed that individuals with and without acne had no major differences in these hormones, but serum estradiol levels were higher in acne patients. This might trigger other thymic hormones which cause acne outbreaks as an inflammatory response to sebum production or infection with Propionibacterium acnes.
Another hormone which might play a role in the pathogenesis of acne is luteinizing hormone (LH) which seems to have a more sustained period of action in a subsection of male patients than in unaffected males. In most males, LH falls steadily over time as growth occurs. Another study suggested that in acne patients, LH levels determine serum testosterone levels, and therefore correlate with acne outbreaks. This subgroup of men with chronic acne is either hyperresponsive to LH, or has a greater total mass of androgen-secreting glandular tissue.
Oral contraceptives have proven to be of benefit in some girls because they reduce androgen production as a result of suppression of pituitary gonadotropin secretion. In males, danazol may play the same role without the associated estrogenic effects, because it also inhibits gonadotropin production. It is currently used to treat refractory male acne when topical agents and systemic antibiotics have not proven successful. However, the effect is limited to the time the patient is on the drug, as acne promptly rebounds when it is stopped. Side effects are usually mild in males, though the drug can cause androgenization in females.
Another useful drug is the antiandrogen cyproterone acetate. It inhibits sebum production, and thus prevents acne outbreaks. However, it is not used as a first-line treatment. Furthermore, it may cause breast lumps, which resolve when treatment is stopped. Its effects are not permanent, however, and relapse is extremely common.
A cautionary note is in order regarding the use of tetracycline in severe acne. Though effective in clearing comedones, some research has exposed an unexpectedly higher risk of prostate cancer in treated men. The contribution of tetracycline to the pathogenesis of this condition in men with acne is yet to be fully elucidated.
Reviewed by: Dr Tomislav Meštrović, MD, PhD