Guest post by Dr. Fiona McCulloch
PCOS is a condition that comes in many different variants, with each woman expressing symptoms in a unique way. Androgen excess is often a central factor in PCOS – most women express either clinical signs of it including acne, hirsutism or androgenetic alopecia, or have lab work with high levels of hormones like testosterone, androstenedione, 17-OH Progesterone, DHEA-S or dihydrotestosterone.
One of the most pronouncedly unique expressions of PCOS involves women who have high levels of a hormone known as DHEA-S. This androgen is only produced by the adrenal glands, and it’s been found that women with high DHEA-S have rather different characteristics than other women with PCOS. In general, androgenic hormones can come either from the adrenal glands, or from the ovaries. As both the ovaries and adrenals come from the same basic type of tissue as an embryo is developing, they can also form similar types of hormones later on in life.
Up to 50% of women with PCOS have high levels of the adrenal hormone DHEA-S in their blood. This can easily fly under the radar because the DHEA-S reference ranges on standard blood tests are very large and don’t reflect the natural drop of this hormone which occurs with age. DHEA-S levels are relatively high at birth because these hormones enter the fetal circulation from the mother. Afterwards, they drop and remain low throughout early childhood. At around age 9-11, most children undergo a process called adrenarche, where the adrenal glands activate before menstrual periods start.
Along with adrenarche comes a period of natural insulin resistance to help build extra fat in the body, preparing a girl for reproduction. A young woman’s DHEA-S levels continue to rise until the early to mid- 20s when they reach a strong peak – around age 30 they then begin to decline steadily throughout life.
In a woman with adrenal androgen excess PCOS, this normal pattern ends up disrupted. Often, DHEA-S levels are above the reference range when compared to other women without PCOS of the same age. DHEA-S levels can also fluctuate greatly in women with this type of PCOS, whereas in other women they tend to steadily decline with age.
What Causes Adrenal Androgen Excess PCOS?
Mystery still remains when it comes to the cause of adrenal androgen excess PCOS. That said, we know that early-onset adrenal activation in young girls definitely increases the risk of developing PCOS in women by around 50%. Symptoms of premature adrenarche include early appearance of pubic or underarm hair, and underarm sweating.
The main stimulator of DHEA-S production in the ovary is the same brain derived hormone that stimulates the production of our main stress hormone, cortisol. This hormone, known as ACTH is released when we experience stress, and has an important function in the body. In women with adrenal androgen PCOS however, it also causes excessive androgen release. Women with PCOS are known to secrete more of the stress hormone cortisol. It’s possible that this could result in increase pituitary output of ACTH to keep cortisol levels regular.
Another cause proposed for adrenal androgen excess is high levels of stress during the development of a fetus. This might be more common in PCOS but it’s also important for women to know that they likely couldn’t prevent PCOS in their children – it’s a complex condition with environmental and genetic triggers.
Overall, it seems that the tendency to oversecrete DHEA-S is familial in nature. Some studies have found that levels of DHEA are inherited in a family by up to 67%.
Benefits of Adrenal Androgen Excess PCOS
Benefits? Yes, that’s right – the adrenal variant of PCOS does come with some benefits. Insulin resistance is a major aggravating factor to most women with PCOS. However, those with adrenal androgen excess may be at least in part protected to more significant metabolic struggles. Overall, elevated adrenal androgens appear to provide protection from cardiovascular risks and insulin resistance, and not surprisingly adrenal androgen excess is found more often in lean women with PCOS, though this is not a rule and it can be present in any woman.
Other benefits of this type of PCOS can appear with age, as adrenal androgens reduce in time for women, making many of the challenges of excess testosterone diminish. DHEA-S can increase reproductive time-span and muscle strength with age in women. In fact, many women who are trying to conceive in their later years take supplements of DHEA to increase the functioning of their ovaries – many women with PCOS already have this natural advantage!
Which tests should I ask for to understand if adrenal androgen excess is an issue for me?
The most useful tests to request include:
- DHEA-S (androgen made only by the adrenals – positive sign of adrenal androgen excess particularly in women over 30). See figure for typical levels for age in PCOS. If high for age, this is a sign of adrenal androgen excess.
- Total Testosterone (primarily made by the ovaries)
- Free Testosterone (insulin resistance makes this marker higher, leaving more testosterone free to activate receptors)
- Cortisol (early morning) – women with adrenal androgen excess who have higher cortisol levels need to address their stress levels more intently.
- Cortisol – urinary 24 hour – over a whole day women with adrenal androgen excess who secrete more cortisol need to address their stress levels more intently
- Cortisol – salivary diurnal – 4 measurements of saliva cortisol throughout the day can provide information on adrenal function compared to the typical circadian pattern.
These tests should be able to find adrenal androgen excess PCOS, and help to rule out a rare condition which mimics PCOS which is known as non-classical congenital adrenal hyperplasia. Many women with all types of PCOS can have high levels of 17-OH Progesterone, but women with non-classical CAH tend to have markedly high levels. If this is the case, a ACTH stimulation test should be ordered by the doctor to make a definitive diagnosis.
What can I do for Adrenal Androgen Excess?
First, because the same hormone that triggers the release of cortisol (ACTH) causes DHEA-S to be released as well – we want to make sure we have normal, healthy cortisol patterns. This means keeping stress managed of course, but to go even further, it means having a healthy circadian rhythm.
A normal healthy pattern of cortisol is high in the morning and then declines throughout the day until it becomes low at night. Cortisol stays low at night, which allows us to stay asleep. Then, it rises again in the morning to wake us up. As such, sleep – quality, quantity and timing should be prioritized for women with adrenal androgen excess.
7-8 hours per night is optimal and it’s helpful to get to bed by 10pm if possible. Allow yourself to wind down and get off the devices as the crisp blue light can cause problems with your brain’s perception of day and night.
Another consideration that is particularly important is the regulation of blood sugar. When blood sugar drops, cortisol rises – stimulating the adrenal gland. Keeping blood sugar regulated and avoiding hypoglycemia is key.
Combining protein with healthy fats at meals along with high fiber vegetables can help keep blood sugar stable between meals.
In particular, for those with adrenal androgen excess, timing your carbohydrate intake can be helpful. A breakfast with protein and healthy fat, with low glycemic index carbs like berries keeps blood sugar stable to start off the day. Lunch may include a little more carbs, but at dinner is when it may be best to have a moderate (3/4 cup) serving of starchy carbs like sweet potato, butternut squash, or buckwheat. The carbs at this time fill the glycogen tank of the liver, helping to keep blood sugar stable while you sleep.
Supplements and Treatments
Many supplements can be beneficial for the treatment of adrenal androgen excess once diet and lifestyle are managed well. The most important basic nutrients are key particularly if stress levels are high.
Fish oil (Omega-3 Fatty Acids)
A high quality fish oil can help alleviate activation of the hypothalamic-pituitary-adrenal axis through decreasing inflammatory mediators (Liu, 2013). Omega-3 Fatty acids can also reduce activation of the HPA (stress) axis and decrease activation of ACTH during stress (Liu, 2013. Jiang 2012). ACTH is the main stimulator of DHEA-S release so this is crucial for women with PCOS.
An example of an adaptogenic herb, is rhodiola, also known as golden root – and there are a variety of ways to use these herbs to treat adrenal conditions. The active ingredient in rhodiola, salidroside, has been found to reduce the expression of CRH in the brain and significantly reduce the levels of cortisol, thereby improving depressive symptoms and regulating the HPA axis(Yang, 2015). Rhodiola improves stress responses in the brain occurs in response to stressful stimuli, particularly those that result in feeling low mood or depression.
Vitamin B5, and Vitamin D – Micronutrients and Microbiome
Looking at micronutrients, Vitamin B5 (Pantothenic acid) is a key factor in adrenal regulation. This important B vitamin is often produced in significant amounts by our friendly gut microbiome, like many of the other B complex vitamins. We need Vitamin B5 for adrenal function and for the production of cortisol. It’s been found that pantethine (a form of B5) can buffer the increase in corticosteroids stimulated by ACTH, the same hormone that activates excess androgen production during stress.
Interestingly, vitamin D deficiency can change the gut microbiome, reducing our natural production of pantothenic acid, which not only results in deficiency, but can also adversely affecting the immune system and produce a pro-inflammatory state (Gominak, 2015). Research has also found that seasonal fluctuations in vitamin D levels can shift towards a microbiome that promotes weight gain in winter when vitamin D is deficient and that supplementing with a b complex along with vitamin D can help to restore beneficial microbes (Gominak, 2015).
Humans have always had a commensal relationship with their microbiome, with us providing them the vitamin D they need, and they providing us B vitamins that we require. We know that women with PCOS tend to have an altered intestinal environment with reduced amounts of metabolically beneficial species year round – but also, women with PCOS have increased likelihoods of having deficient vitamin D.
When pantothenic acid is deficient, it can decrease a neurotransmitter called acetylcholine which is a key factor in the parasympathetic nervous system – our portion of the nervous system that is most active in a state of relaxation (Pietrocola, 2015). Without the opposition of the parasympathetic nervous system, the sympathetic nervous system (flight-or-fight) becomes predominant and triggering of the HPA axis occurs, resulting in further aggravation of adrenal androgen excess.
This is a small peek into the world of how our hormones connect with our gut microbiomes and our brains, many factors are present to help keep us balanced and healthy. With adrenal androgen excess type PCOS, most women also display many other characteristics of PCOS as well, and this is why each and every woman with PCOS is completely unique!
Gominak SC. Vitamin D deficiency changes the intestinal microbiome reducing B vitamin production in the gut. The resulting lack of pantothenic acid adversely
affects the immune system, producing a “pro-inflammatory” state associated with atherosclerosis and autoimmunity. Med Hypotheses. 2016 Sep;94:103-7.
Liu, Y., Chen, F., Li, Q., Odle, J., Lin, X., Zhu, H., … Shi, H. (2013). Fish oil alleviates activation of the hypothalamic-pituitary-adrenal axis associated with inhibition of TLR4 and NOD signaling pathways in weaned piglets after a lipopolysaccharide challenge. The Journal of Nutrition, 143(11), 1799–807
Jiang, L.-H., Liang, Q.-Y., & Shi, Y. (2012). Pure docosahexaenoic acid can improve depression behaviors and affect HPA axis in mice. European Review for Medical and Pharmacological Sciences, 16(13), 1765–73.
Panossian A, Hambardzumyan M, Hovhanissyan A, Wikman G. The adaptogens rhodiola and schizandra modify the response to immobilization stress in rabbits by suppressing the increase of phosphorylated stress-activated protein kinase, nitric oxide and cortisol. Drug Target Insights. 2007;2:39-54.
Pietrocola, F., Galluzzi, L., Bravo-San Pedro, J. M., Madeo, F., & Kroemer, G. (2015). Acetyl Coenzyme A: A Central Metabolite and Second Messenger. Cell Metabolism, 21(6), 805–821. http://doi.org/10.1016/j.cmet.2015.05.014
Yang SJ, Yu HY, Kang DY, et al. Antidepressant-like effects of salidroside on olfactory bulbectomy-induced pro-inflammatory cytokine production and hyperactivity of HPA axis in rats. Pharmacol Biochem Behav. 2014;124:451-457.
Dr. Fiona McCulloch, is the founder and owner of White Lotus Integrative Medicine, one of the longest established integrative medicine clinics in Toronto Canada. Fiona has worked with thousands of people seeking better health over the past 16 years of her practice. She is also committed to health education and to sharing the most current information on health topics, nutrition and natural medicine with patients and other practitioners.
Fiona has published many articles and is a regular contributor to NDNR, one of the leading journals for naturopathic doctors as well as other publications for health professionals. Her first book “8 Steps To Reverse Your PCOS” will be published on September 21st, 2016 for PCOS Awareness Month.
As a woman with PCOS herself, who struggled for many years with irregular cycles, cystic acne and metabolic issues, she’s passionate about health education and advocacy for women with PCOS, and serves on the medical advisory committee of the PCOS Awareness Association and as an expert on IVF.ca. She is also a medical advisor to The Open Source Health Precision Medicine PCOS Project which integrates genetic and molecular testing, and evidence-based integrative medicine and cloud-based technology to help the growing community of women with PCOS.
Fiona also frequently lectures to patient groups as well professionalsm including naturopathic doctors and integrative medicine clinicians and also to students at the Canadian College of Naturopathic Medicine.
Fiona is a graduate of the Canadian College of Naturopathic Medicine (2001) and the University of Guelph (Biological Science/Molecular Biology and Genetics).