PCOS and Acne

The incidence of Acne in women with PCOS is reported to be around 20 to 40%. In PCOS, while many women exhibit facial acne, some women have reported to have acne in the neck, chest and upper back regions. Acne being one of the worrying cutaneous manifestations of PCOS is different from acne vulgaris which is common in adolescents and usually remits by the third decade of life. Unlike in normal women, there is increased receptor sensitivity to circulating androgens in women with PCOS. Correlation of acne with high levels of Dehydroepiandrosterone Sulphate (DHEA-S), DHT, androstenedione, testosterone and IGF in women with PCOS have been established. Androgens increase sebum production, causing abnormal desquamation of follicular epithelial cells that result in formation of comedones. Colonization of abnormal follicles results in inflammation and further formation of papules, pustules, nodules, cysts and scarring. Persistent adult acne and post-acne pigmentation might leave psychological effects on women  especially among professional or working women.

Presence of acne in women with PCOS may be associated with certain clinical, hormonal and biological factors. Acne is a cutaneous symptom of hyperandrogenism characterized by excessive levels of male sex hormones, typically testosterone in the female body. In PCOS, high serum testosterone has been more commonly associated with acne. Testosterone levels should be measured in women presenting with acne, especially in women who are treatment-resistant. Elevated testosterone levels are treated with anti-androgen therapy. If total testosterone is elevated, further testing for free testosterone, sex hormone binding globulin (SHBG) and other androgens are advisable.

It is not necessary that all women with clinical signs of  hyperandrogenism have elevated circulating androgen levels. Acne in women with normal androgen level in the blood can be either due to increased responsiveness, in other words hypersensitivity of the pilosebaceous glands to the normal androgen level or increased activity of an enzyme that converts testosterone to dihydrotestosterone which is a sex steroid that is five times more potent than testosterone. Skin follicles have different levels of susceptibility to circulating hormones causing some follicles to be more prone to acne than other follicles. Acne pathophysiology  in women with PCOS explains alternative mechanisms of increased sensitivity of the sebaceous gland to androgens and the increased metabolization of local androgen hormones into potent androgen metabolites.

In a study from south India, 76 percent of women were found to be vitamin D deficient. Vitamin D is a fat-soluble prohormone steroid with endocrine, paracrine and autocrine functions. Physiological role of Vitamin D in reproduction includes ovarian follicular development and luteinization. Vitamin D alters AMH signalling, FSH sensitivity and progesterone production in human granulosa cells that significantly correlates with insulin resistance in women with PCOS. There are several studies that support the theory that vitamin D has a functional role in acne development. The identification of vitamin D receptors in human sebocytes and the modulation of lipid and cytokine production by vitamin D suggests a possible association between vitamin D and acne pathophysiology. Vitamin D could be considered an effective tool for modulating acne. Vitamin D(3) supplementation is also shown to improve postprandial insulin sensitivity. The level of 25 Hydroxy Vitamin D has been inversely associated with the severity of acne and there is a significant negative correlation between 25 Hydroxy Vitamin D levels and the development of inflammatory lesions.

Acne as a common component of PCOS and hyperandrogenism, is linked to insulin resistance (IR). IR increases during puberty and appears to be related to fat accumulation. The insulin receptor belongs to the family receptors that includes insulin-like growth factor (IGF). A high concentration of insulin results in the direct and indirect activation of IGF-1 receptors in keratinocytes and fibroblasts, leading to their proliferation and formation of comedones. Fasting insulin levels and HOMA (Homeostatic Model Assessment) are the insulin resistance tests that show significantly higher correlations in women with acne compared with women without acne. Hyperinsulinemia increases ovarian androgen, IGF-1 and IGF-2 production in the liver. Insulin and IGF-1 increase the activity ovaries to produce more androgens. Indirectly, insulin potentiates the action of LH in the ovaries. Another effect of hyperinsulinemia is a decrease in the production of the IGF-1 protein in the liver. This protein is necessary for carrying the sex hormones. This deficiency of the protein contributes to greater action of free testosterone and IGF-1, respectively, in target cells. Hyperinsulinemia is also known to increase the action of 5α-reductase, leading to increased conversion of testosterone into dihydrotestosterone. Oral Glucose Tolerance Test (OGTT) with HOMA IR calculation can be used to diagnose insulin resistance in women with PCOS and acne.

Excessive production of Anti Mullerian Hormone (AMH) secreted by growing follicles is a feature of PCOS. FSH and LH testing is dependent on the menstrual cycle but the menstrual cycle has minimal influence on AMH. AMH testing is useful for diagnosing PCOS in patients with persistent acne. As serum AMH level is correlated with the severity of acne in PCOS,  raised AMH should require an ultrasound for PCOS. Hyperprolactinemia is defined as fasting levels of above 25ng/mL prolactin in women. Women with hyperprolactinemia might present with acne as the sign of chronic hyperandrogenism due to high free testosterone levels in PCOS.

Topical medications for acne are benzoyl peroxide, salicylic acid and sulphur based. These ingredients may help with mild breakouts of acne but may not be effective with hormonal acne as in PCOS. PCOS-related acne can be cleared only by treating the underlying problems of hormonal and metabolic imbalances. Evaluation and management of cutaneous manifestations of PCOS can play a key role in PCOS diagnosis and management. Knowing the markers that indicate abnormalities can guide to the correct acne treatment approach. A patient with insulin resistance should be counselled about life style modifications such as weight loss, exercise and the consumption of a low glycaemic diet. Metformin is the common drug of choice that controls symptoms of PCOS including acne. Myoinositol supplements improve insulin sensitivity in PCOS patients that can also prevent cutaneous inflammation. Oral contraceptives with antiandrogenic progesterone are also advised for women with PCOS who are experiencing irregular menstrual cycles, that seems to have control on the manifestation of acne as well. Vitamin D supplementation is known to positively help treat acne directly or indirectly by improving insulin sensitivity and reducing hormone dysfunction.






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