Acne in Adult Women
Acne vulgaris in adult women - Clinical understanding through an altered androgenic lens
by Dr. Laura Neville
Background:
Acne vulgaris is often a sign of underlying metabolic disturbance – a web woven of blood sugar, insulin, and sex hormone imbalance and often also a signal of microbiome disturbance. Classically, insulin resistance leads to direct stimulation of androgens from the ovaries in females. Overproduction of testosterone may lead to excessive sebum production, which, in turn, may increase the risk of inflamed sebaceous glands. This can trigger acne outbreaks.
Salivary hormone testing often reveals elevations in testosterone and or DHEA in women suffering with acne. Salivary hormone testing is sensitive enough to capture elevations in testosterone and or DHEA prior to overt changes in glucose or insulin levels captured through blood testing which makes it a powerful tool to identify and intervene before more overt pathologies, such as PCOS, metabolic syndrome, or type 2 diabetes develop and become harder to resolve.
But what about cases where objective tests measurements all appear to be normal?
Female Adult Acne:
Adult female acne seems to present in normoandrogenic women (meaning normal free testosterone levels), unlike most adolescent cases. Clinically, these adults have moderate acne involving the lower face and lateral neck in contrast to adolescents, who typically present with frontal area, nose, and malar area lesions.
One theory describes local glandular metabolism of the skin increasing the production of sebum, leaving these areas more prone to and increasing the colonization by Propionibacterium acnes (P. acnes). During peripheral conversion, the sebaceous gland can transform weak hormone precursors into potent androgens such as testosterone and DHT as its cytoplasm contains all the six enzymes needed for androgenic amplification. Only a minimal amount of the potent intracellular androgenic products reach circulation; the major action is restricted to the sebocytes. Moreover, studies have demonstrated an increase in 5α-reductase activity and higher androgen receptors expression in sebocytes so that even with normal androgenic levels, sebaceous glands may be hyperactive.
A study in adult women, ages 26-44 with mild to moderate acne but not hirsutism, androgenetic alopecia nor irregular menses, revealed that the androgen metabolite androsterone glucuronate (measured via solid phase extraction and quantification by liquid chromatography associated with sequential mass spectrometry/LC-MS/MS in blood samples) was the only significant marker differentiating control and acne groups. No differences were observed in the levels of total testosterone, free testosterone and DHEA-S among the study participants. Thus, the study, among others, concludes that the typical biomarkers for hyperandrogenism are not useful in adult patients with isolated acne and that the level of androsterone glucuronate is preferred because it reflects total androgenic metabolism and peripheral conversion. Another important aspect of this study was that the androsterone glucoronate levels were reduced in the treatment arm alongside lesion improvement, suggesting a potential clinical measure of treatment efficacy.
Metabolism, Excretion and Therapeutics:
In the end, androgens need to be metabolized into water-soluble substances to be excreted. Thus, all androgens, regardless of production site, are eliminated by sulfation and glucuronidation processes. Glucuronidation enzymes are called UDP-glucuronosyltransferases (UGTs) and are found throughout the body, the majority in the liver as it is key organ of detoxification for internal compounds such as hormones.
Sulforaphane, found in cruciferous vegetables (with the highest levels in broccoli sprouts), increases glucuronidation, as does green tea. Green tea is especially rich in epigallocatechin gallate (EGCG), a polyphenol that has shown to improve acne. In addition to having anti-inflammatory, antioxidant, and antimicrobial properties, EGCG lowers lipid levels and is anti-androgenic.
Other substances shown to induce UGTs include soy foods, resveratrol, and citrus foods, along with rooibos and dandelion teas, rosemary, curcumin, and astaxanthin. Magnesium is also critical for sulfonation, glucuronidation and glutathione conjugation reactions.
In Summary:
If testosterone and/or DHEA levels appear normal either in serum or saliva, consider androgen metabolite testing to understand levels reflective of sebocyte peripheral conversion. Depending on the case, treatment to reduce androgenic activity, modulate metabolism, inhibit enzymes and/or reduce local peripheral conversion may be in order.
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