INL Articles: How do hormones affect the skin?

Acne vulgaris and the Endocrine system: How do hormones affect the skin?

Most of us think that pimples are for teens. Not so. The average age is no longer 20, rather 26. Acne, especially adult female acne (AFA), is increasing in prevalence, hindering quality of life, along with marked negative social and psychological impacts.

Among the clinical symptoms, comedones, papules and pustules, acne has been found to adversely affect the social life, self-esteem and body image of individuals and is often seen with some level of depression and anxiety as concomitant presentations. (1) Socially, significantly higher unemployment rates have also been observed in studies among acne cases relative to controls, suggesting real social impact.

Women have a higher prevalence and incidence for acne than men, especially after 25 years of age. (2)  Whilst there can be multiple origins for its development, often if it is hormonal in nature, we find that polycystic ovarian syndrome (PCOS) is the main cause. This is especially the case it seems, in women over 25. Interestingly though, we would also see hirsutism and acanthosis nigricans present as concomitant symptoms along with the acne; the acne would rarely present on its own. Abdominal weight gain associated with insulin resistance may be associated.

In this edition of our newsletter we look more deeply into PCOS and one of its symptoms - acne.

How does the endocrine system play a role in acne vulgaris?

At around 8 years of age, androgens (male hormones) are produced from the adrenal glands with the amount produced gradually increasing during puberty. As the androgen levels increase, the sebaceous glands respond by producing more oil (sebum) so much so that whiteheads (closed comedomes) can actually develop in younger, prepubescent children.

As puberty begins, boys have higher levels of androgens than girls. As the sebum levels increase in response to the androgen levels, bacteria which normally live on the skin surface, digest the oil and the by-products irritate the skin, blocking the pores leading to blackheads, pimples and cysts.

It is well-documented that the bacteria, Propionibacterium acnes, also contributes to this problem by accumulating in the ducts, further contributing to the inflammation that is a hallmark of acne vulgaris.

With the potent androgenic combination of dihydroxytestosterone (DHT) and testosterone, insulin is also a major player both in the pathogenesis of the hormonal irregularities as well as contributing to the growth and maturation of the sebaceous glands. This happens via the upregulation of growth hormone receptors. (3) Insulin plays a further role in the positive feedback effect on adrenal and ovarian androgenesis via inhibiting SHBG production from the liver. Both testosterone and Insulin levels are often, but not always, both associated with PCOS.

This then leads to a sequential, although controversial, link between diet and acne that can explained by high glycemic foods increasing insulin release, which in turn, results in excess androgen and sebum production in women. (4)

Couple a high glycemic diet or simply a high carbohydrate diet with the higher stress levels also tending to elevate insulin levels, and if clinically relevant we see a further increase in androgen production from the adrenal glands, compounding the issue.

Indeed, insulin affects the androgenic state not only directly by interfering with metabolism of ovarian and adrenal androgens, but also indirectly by decreasing circulating SHBG levels. SHBG is a protein that binds to testosterone, making it unavailable to target tissues. Higher levels of SHBG lead to lower bioavailability of testosterone, thus minimizing the hyperandrogenic features. Furthermore, SHBG appears to be a potentially valuable marker of Insulin Resistance in PCOS. (5)

Herbal medicine can be a potent regulator of the hormones involved in the proliferation of acne

With pharmaceutical options to assist with the multi-faceted presentation of androgen dominance sometimes limited, herbal medicine can often fill the gap required with the use of combined herbs in specific formulas.

A combination of Peonia lactiflora and Glycyrrhiza glabra has decreased serum testosterone as well as other features of acne vulgaris

This combination of herbs has been used in traditional Chinese and Japanese herbal medicine and has been referred to under the following names: Shaoyao Gancao Tang (Chinese), Shakuyaku-Kanzo-To (SKT, Japanese) and TJ-68 (a Japanese proprietary product).

As the formula SKT, administered at an equivalent dose of 4-6g of dried Paeonia root and dried licorice root over periods ranging from 2-8 or 24 weeks, significant decreases in serum testosterone in women with defined PCOS were seen. (6) In some cases, regular ovulation was established and some women conceived. This same trial also expressed that no side effects were observed.

In another study this time with women with acne vulgaris, SKT, given at higher dose than the previous study (equivalence of 6g of dried Licorice and Paeonia root) for 12 weeks, a significant decrease in serum free testosterone was also found when compared with baseline values. As a further bonus, the herbal treatment also significantly decreased the number of comedones, the primary lesions of acne vulgaris. (7)

Vitex Agnus Castus can assist with hyperprolactinemia and improve progesterone status

Whilst androgens are the key focus here, there is also good evidence suggesting that acne genesis can be stimulated by hyperprolactinemia. (8)

Hyperprolactinemia is considered to be one of the more frequent causes of cyclical disorders including corpus luteal insufficiency. A consequence of this is premenstrual syndrome and importantly, progesterone deficiency, which is a competitive inhibitor of 5-alpha reductase and might reduce gland activity in acne vulgaris.

In an uncontrolled study, Vitex reduced elevated prolactin levels in 80% of 34 women with hyperprolactinemia at a dosage of 30-40mg per day for one month, well below the normally recommended dosage period of 3-6 months. Improvements in the symptoms was demonstrated in a variety of menstrual disorders, most notably correction of progesterone deficiencies. (9)

And so, it seems that herbal medicine can play an evidence-directed role in the management and pathogenesis of acne vulgaris especially when there is a hormonal or endocrine origin.

The added role of B-vitamin derivatives in the management of the hormone/skin axis

We can briefly mention here one nutritional supplement that, along with a low GI Diet can further assist the PCOS-Acne problems: Myo-inositol and Chiro-Inositol

Myo-inositol (MI) is one of the most commonly used isoforms of a B related vitamin called  inositol, the other being D-Chiro Inositol (DCI). MI and DCI balance in different ways some metabolic deregulations concurring with insulin resistance (IR). (10) Insulin resistance and consequent hyperinsulinemia are related to many aspects of the PCOS such as hyperandrogenism, reproductive disorders, acne and hirsutism. Besides metformin, MI is now considered as a further insulin-sensitizing supplement which can benefit women with PCOS. (11) (12)

Treatment duration seems crucial, as far as androgen profile is concerned. This agrees with the previous observation on acne, whose improvement with MI required at least 6 months supplementation. (13)

Inositols are involved in the postreceptor signal transmission of several receptors, such as insulin, follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH), and MI-derived phosphoinositol-3-phosphate (PIP3) enhances glucose transport inside the cells through the stimulation of GLUT4 translocation to the cell membrane.

DCI upregulates pyruvate dehydrogenase leading to the production of ATP by the Krebs’ cycle. MI and DCI promote glycogen synthase, inducing glucose conversion to glycogen stored inside cells. MI modulates the activation of glucose transporters and glucose utilization, and glycogen synthesis takes place under the control of DCI. (14)

DCI on the ovary regulates the insulin-induced androgen synthesis, whereas Myo inositol regulates glucose uptake and FSH signaling. One study shows the ability of a combination of ALA (Alpha Lipoic Acid) and Myo inositol to restore a normal menstrual cyclicity in women with PCOS in 72% of cases. The response rate was 85.7% of women taking 2000mg of Myo- inositol. (15)

Myo-inositol has also assisted with improvements in the associated hirsutism and acne associated with PCOS after 6 months of treatment. This was also seen with significant reductions in plasma LH testosterone, free testosterone, insulin and HOMA index. (16)

Other Factors in Acne

Emerging evidence suggests that the connection between the digestion and the skin via the gut-skin axis is also more pronounced than originally thought. For example, one study involving 13,000 adolescents showed that those suffering from acne were more likely to experience gastrointestinal symptoms such as constipation, bad breath and gastric reflux. Furthermore, abdominal bloating was 37% more likely to be associated with acne and other forms of seborrheic diseases. (17)

Importantly, the support of the lymphatic system and digestion would also be recommended when looking at the use of natural medicine as well as the more potent nutritional interventions that can support the symptomatic attenuation of the symptoms.

We’ll be exploring the gut-skin connection and the benefits of herbal therapies further in our next newsletter!

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