Polycystic ovarian syndrome and hair loss
Polycystic ovarian syndrome and hair loss

WHAT IS PCOS ?

Polycystic ovarian syndrome (PCOS) is a condition where the ovaries become enlarged and develop fluid-filled sacs surrounding the eggs that are usually released during ovulation.

Common symptoms of PCOS are hair loss, decreased fertility, irregular periods, insulin resistance, high dehyroepiandrosterone, high free testosterone, acne and excessive body hair.  Women with PCOS tend to have a cluster of metabolic abnormalities including obesity, impaired glucose tolerance and a high level of free fatty acids in the blood.

PCOS is associated with a higher level of inflammation markers such as C-reactive protein, white blood cells, tumour necrosis factor-alpha (TNF-a), interleukin-18 (IL-18) and interleukin-6 (IL-6).  The diagnosis and management of PCOS can be complicated by low thyroid function and impaired iron metabolism.

Lifestyle modification can reduce the severity of PCOS symptoms, however 45% of women with PCOS have reported they have never been provided with information about lifestyle management.  Additionally, zinc supplementation has a beneficial effect on hair loss and excess body hair associated with PCOS.

PCOS symptoms and hair loss

WHAT CAUSES PCOS?

The exact cause of PCOS is unknown, but research links PCOS to an abnormal hormone balance.  Blood tests often show women with PCOS have a higher level of testosterone, follicle stimulating hormone, luteinising hormone, prolactin and low levels of sex hormone binding globulin (SHBG).

Whole genome association studies, focused on women from Asian and European populations, found several common genes associated with PCOS, but the relationship between the genes and the development of PCOS is unclear. Another study on the relationship between the characteristic traits of PCOS and susceptibility genes found no relation with insulin sensitivity, menstrual events and ovarian volume.  This study was able to pinpoint a protein in humans encoded by the follicle-stimulating hormone beta subunit was significantly associated with free testosterone and levels of luteinising hormone.

PCOS is a highly complex disorder influenced by genetics and environmental factors.  Whilst several genes contribute to the pathogenesis of the disease, insulin resistance, plays a key role in the development and severity of the disease.

Causes of PCOS

INSULIN RESISTANCE IS A KEY DRIVER OF PCOS

Insulin resistance and elevated blood glucose are found in up to 75% of women with PCOS.  High levels of insulin are an important factor in the maintenance of high testosterone and high levels of luteinising hormone normally seen in PCOS patients.  Insulin resistance accounts for the high levels of obesity, glucose intolerance, and type II diabetes found in women with PCOS.

High levels of insulin suppress levels of SHBG due to the inflammatory and metabolic processes involved in the progression of hyperinsulinemia.  SHBG is a glycoprotein manufactured in the liver for storage of testosterone and estrogen in the blood.  When testosterone is bound by SHBG it has no biological activity.  Two women can have the same level of total testosterone, but one can have a higher free level of testosterone due to lower SHBG.  Higher levels of free testosterone will increase PCOS symptom severity.

In females, around 50% of testosterone is produced in the ovaries and 50% from the adrenal glands.  Most adrenal testosterone in females is converted to estrogen by an enzyme called aromatase.  For normal aromatase activity, the blood concentration of insulin must be below 10 ng/ml.  Higher concentrations of insulin in the blood reduce aromatase activity, at 100 ng/ml there will be no activation of aromatase.

Biological functions are mostly managed by feedback loops, where levels of hormones are monitored to stop them from becoming too high or too low.  High levels of insulin disrupt this feedback loop which then disrupts the activity of follicle stimulating hormone and luteinising hormone.  Follicle stimulating hormone production is stimulated by testosterone from the ovaries, but when aromatase activity is repressed, it is also produced in the presence of testosterone from the adrenal cortex.

Where testosterone cannot be aromatased to estrogen, it will be upconverted to dihydrotestosterone, a potent and biologically active metabolite of testosterone.DHT exposure induces the reproductive PCOS traits of menstrual cycle irregularity and ovulation dysfunction.  DHT also increases fasting glucose levels and increases fat accumulation.  Insulin resistance testing will not take into account organ specific insulin resistance, such as the resistance in the liver due to visceral fat.

VISCERAL FAT AS A MARKER OF INSULIN RESISTANCE IN WOMEN

Whilst obesity is a common symptom of PCOS, many women with the condition are of normal weight, with blood tests that report normal insulin sensitivity.  Insulin resistance is a common but not universal marker of PCOS.

Isolated insulin resistance cannot be reliably diagnosed, as fasting insulin reflect insulin secretion and clearance as well as insulin resistance.  Other diagnostic methods where the PCOS patient gives a fasting blood sample (such as fasting glucose insulin ratio and quantitative insulin sensitivity check) are all based on fasting glucose and insulin levels, essentially providing the same information.

It is widely accepted that visceral fat in the abdominal area mediate insulin resistance.  A study by Bergman et al in 2006, found free fatty acids are among the most important products of visceral fat to promote insulin resistance.  The anatomical position of visceral fat in the abdominal area plays an important role in the pathogenesis of insulin resistance.  Visceral fat initially increases rapidly when body fat increases before reaching a plateau, extra fat is then stored in subcutaneous tissue. Researchers found that moderate abdominal fat resulted induced liver insulin resistance while sensitivity to insulin remained normal in other tissues.  When levels of body fat increases, insulin sensitivity is reduced in other tissues.

The level of subcutaneous tissue determines overall obesity.  This explains why visceral fat can contribute to insulin resistance in normal weight and obese women with PCOS.  By measuring the gene expression of a variety of enzymes important to the liver and subcutaneous fat, they found the overall expression of enzymes related to fat turnover in visceral fat increased when any fat is ingested.  The free fatty acids released by fat turnover were found to be responsible for insulin resistance in the liver.  Free fatty acids are a potent stimulator of insulin secretion and can reduce the clearance of insulin by the liver, both of which may contribute to high levels of circulating insulin [1].

HOW IS PCOS LINKED TO HAIR LOSS?

When sex hormone balance is disturbed, and there is an increase of testosterone, this often leads to a condition known as androgenic alopecia.  High levels of circulating testosterone can lead to a rise in DHT under specific conditions.  When DHT is present in hair follicles, the hair on the scalp grows for a shorter duration of time and becomes thinner in diameter, hairs on the rest of the body grows thicker and longer.  Whilst this type of hair loss is common, research shows that hair loss affects less than 40% of women with PCOS.

In addition to this type of hair loss, high levels of circulating glucose and insulin caused by insulin resistance increase blood vessel wall thickening and stiffening.  Hair follicles rely in a steady exchange of nutrients from the blood.  When blood vessel walls are thicker and stiffer, this lowers nutrient exchange potential, particularly in areas where blood vessels are smaller, such as the scalp.

Hair loss linked to PCOS can have the following characteristics:

  • A wider hair parting with more scalp showing
  • Hair loss mainly in the front and side areas of the scalp
  • Recession at the temples appearing as an increase in ‘baby hair’ or a receding hairline
  • Dry and frizzy hair that breaks easily
PCOS and hair loss diagram

TESTOSTERONE, DHEA, OBESITY AND PCOS

Testosterone and its precursor, DHEA are fat reducing steroid hormones produced from cholesterol.  Normally, a decrease of testosterone and DHEA is associated with a corresponding increase in body fat and LDL cholesterol.  Testosterone and DHEA are both fat reducing hormones, but they exert their effects by different mechanisms.

Testosterone supplies adipose tissue with free fatty acids and promotes the breakdown of fat, indirectly causing a decrease in leptin.  Leptin reduces appetite and body weight, elevated leptin levels with high levels of fat is evidence of leptin resistance.  Testosterone also prevents the development of adipose precursor cells into mature fat cells.

DHEA does not have any of these effects; however, DHEA stimulates resting metabolic rate and enhances glucose disposal by increasing glucose receptors on fat cells.  This insulin-like effect on glucose leads to a marked decrease in insulin concentration.  The fat reducing effect of testosterone and DHEA work on the visceral and subcutaneous fat that causes obesity.

DHT, which is produced from testosterone, does not have the same fat-burning effect of testosterone.  DHT inhibits the breakdown of fat by reducing energy expenditure and fat burning, though it does not decrease appetite.

Women with PCOS appear to have a generalised exaggeration in adrenal steroid hormone synthesis in response to stimulation from adrenocorticotropic hormone (ACTH) without overt hypothalamic-pituitary-adrenal axis dysfunction.  ACTH is produced by the pituitary gland; its key function is to stimulate the production and release of cortisol from the cortex (the outer part) of the adrenal gland.

Cortisol is a steroid hormone that regulates a wide range of process throughout the body including metabolism, glucose levels, immune response and inflammation management.  The pituitary gland will attempt to increase levels of circulating cortisol in between meals where blood glucose is low, when the immune system is activated and to lower inflammation within the body.  It serves to lower energy expenditure by lowering thyroid function when insufficient building material is available.  Building materials for the body provided by the diet such as protein, iron and zinc trigger a release of cortisol.  In addition, skipping breakfast and not eating often leads to a rise in cortisol requirements.

High levels of ACTH, body fat and insulin increase the conversion of DHEA to cortisol and DHT creating a viscous metabolic cycle.

REDUCING PCOS SYMPTOM SEVERITY WITH MEDICATION, DIET AND EXERCISE

Whilst there is no specific cure for PCOS, moderate lifestyle modifications such as an improved diet or regular exercise can decrease symptom severity and help regrow.  In cases where insulin resistance is severe, some medications have been shown to support normalisation of blood glucose levels.  As part of an organised programme aimed at reducing PCOS symptom severity, lowering insulin levels have been shown to reduce testosterone levels, increase ovulation and conception rates.

The thiazolidinediones have been shown to be effective at reducing testosterone levels and increasing insulin sensitivity in controlled clinical trials.  While they are effective, the thiazolidinediones may encourage weight gain and are associated with an increased risk of heart disease.  Metformin, an alternative prescription medication, has been demonstrated to be effective in normalising several common PCOS symptoms by reducing glucose production by the liver.

In cases of PCOS, metformin treatment for 8 weeks can reduce weight, fasting glucose, fasting insulin and reduce the risk of developing type II diabetes.  Whilst metformin is successful at reducing specific symptoms of PCOS, studies show no appreciable reduction in testosterone and some women experience side effects such as bloating, abdominal discomfort, excess gas, nausea and diarrhoea.

A small study evaluated the effect of a low carbohydrate diet in women with PCOS.  In this prospective open-label trial, 20 participants were monitored to compare differences between treatment with metformin alone or metformin treatment while following a ketogenic diet under the guidance of a dietician.  During the study the women in the low carbohydrate group consumed up to 50 grams of carbohydrates per day for 12 weeks.  At the end of the study researchers found a significant reduction in body weight (approximately 2kg) and partial normalisation of estradiol, progesterone and cholesterol levels.  Testosterone, the key biomarker relating to hair loss was reduced by around 30% [2].

This study demonstrates manipulating the diet can be beneficial for women with PCOS.  In the long term, diets that severely restrict carbohydrate intake in favour of protein and fats encourage the development of a fatty liver.  On the other hand, lowering the intake of starchy foods like pasta, lentils, oats, bread and potatoes in favour of fruit, vegetables and high-quality proteins, is a more sensible way to lower blood glucose.  When attempting to lower your intake of starch, avoid foods that contain added starches and sugars.  Starches such as modified maize starch is found in many sauces, low fat food, processed meats and flavoured yoghurts.

Cortisol production and circulation increase the severity of PCOS symptoms.  There are several ways cortisol can be reduced in the longer term.  Levels of cortisol are higher in the morning, eating a healthy breakfast are a great way to normalise levels at the start of the day.  To keep cortisol levels stable throughout the day, keep caffeine intake down and do not skip meals throughout the day.  Maintaining stress levels help towards lowering cortisol, though some stress in life cannot be avoided. By supporting the reduction of cortisol through the diet, this helps alleviate spikes of cortisol due to stressful life events.

Whilst lowering carbohydrates improves several PCOS markers, insulin resistance can be constructively managed by reducing the level of free fatty acids in the blood.   Several studies have looked at the impact of exercise interventions on reproductive functions in women with PCOS.  Exercise has shown to improve menstrual cycle and ovulation frequency in comparison to diet alone or no exercise.

Exercise lowers the levels of free fatty acids by stimulating the production of short chain fatty acids from the microbiota of the gut.  Short chain fatty acids are predominantly metabolised by cells of the intestines and the liver.  Short chain fatty acids lower suppress insulin signalling in fat cells reducing the accumulation of visceral fat, even with a high fat diet.  Several bodies of research have identified that exercise has positive effects on the composition and diversity of gut bacteria.

Reducing PCOS symptom severity

LOW THYROID FUNCTION AND PCOS

Low thyroid function can have a negative effect on the ovaries due the increase in prolactin caused by low levels of thyroid hormone.  Low thyroid function, in most cases, leads to an increase in thyroid stimulating hormone which leads to an increased production of prolactin.

Prolactin then effects the normal balance between luteinising hormone and follicle stimulating hormone.  Prolactin also increases the production of DHEA from the adrenal glands.  This hormone fluctuation can lead to an inhibition of ovulation, an increase in ovarian size and cysts on the ovary.  While this causes very similar clinical features to PCOS, there is no evidence that this leads to PCOS.

The similarities between these conditions requires clinicians to be thorough in differentially diagnosing PCOS when the patient has low thyroid function.

DISTURBED IRON METABOLISM CAN INCREASE PCOS SYMPTOM SEVERITY

Often, patients with PCOS have an abnormal iron profile.  Anemia is common in women with the condition, this has been attributed to prolonged periods of heavy bleeding.  A recent study found that of 60 patients, 35 were anemic.  The patients that were anemic had lower levels of SBHG and higher levels of free testosterone [4].

This data is complicated somewhat by the findings that confirm some women have levels of ferritin, the iron storage hormone.  In a separate case-control study, researchers were able to determine testosterone and ferritin were increased in PCOS.  They found that ferritin levels could be an important predictor in measuring the severity of PCOS [5].

Clinicians may find an individual may suffer from iron deficiency anemia, or anemia of chronic disease.  Anemia of chronic disease is a condition where the body withholds iron from the host when inflammation is present.  Chronic inflammation, where inflammation persists over a long period of time, leads the body to prevent the use if iron to reduce inflammatory events and metabolism.  Determining iron deficiency (where haemoglobin levels below 130 g/L) may prevent the increase of symptom severity over time.

INFLAMMATION AND PCOS

PCOS is associated with low-grade systemic inflammation as evidenced by the elevation of several markers of inflammation such as C-reactive protein, interleukin-6, interleukin 18, white blood cell count and other markers of oxidative stress.  Recent studies are unable to determine exact biomarker counts that would specifically relate to PCOS pathology due to varying levels of obesity in patients that interfere with the analysis of results.

Low-grade inflammation is a key contributor to the pathogenesis of PCOS.  Carbohydrates in the diet are capable of inciting oxidative stress and an inflammatory response in women with PCOS.  This inflammatory response is elicited from immune cells that produce TNF-a, a mediator of insulin resistance.  High levels of androgens increase the sensitivity of immune cells and can activate them even when no glucose is present.

In PCOS, biomarkers of oxidative stress and inflammation are highly correlated with circulating androgens.  Pro-inflammatory signals can upregulate enzymes responsible for testosterone production.  This loop enables the polycystic ovary to produce more testosterone that further increase insulin resistance and inflammation [6].

ZINC SUPPLEMENTATION SUPPORTS NORMALISATION OF HAIR GROWTH ON THE SCALP AND BODY

Zinc is required for many vital biological functions including the reduction inflammation and oxidative stress.  Zinc is also plays a critical role in the metabolic pathway that converts cholesterol to testosterone.  Lower zinc levels slow down the production of DHEA from cholesterol and increases the formation of DHT and cortisol.

Several studies show PCOS sufferers with hair loss had lower zinc levels than healthy controls.  Zinc is an essential part of enzymes that digest dietary protein and molecular machinery that synthesises proteins, such as the hair fibre, from DNA.  Zinc also contributes to carbohydrate digestion to and acts as a bactericide to support a healthy gut bacteria population.  In addition, some investigators have shown an association between low circulating levels of serum zinc and acne.

Zinc deficiency may act as an initiator or protagonist of the underlying metabolic features and mechanism of PCOS by decreasing antioxidant capacity to allow higher levels of oxidative stress, inflammation and by increasing the production of cortisol and DHT.   Zinc also lowers insulin levels by increasing levels of DHEA and reducing TNF-a.

The effect zinc has on SHBG is two-fold.  Zinc supplementation increases the production of SHBG from the liver and prevents the binding of estradiol (an estrogen) but not the binding of testosterone [7].  This means zinc directly decreases the amount of free testosterone available to be upregulated to DHT.

A randomised, double-blind, placebo-controlled trial looked at the effects of zinc supplementation in women with PCOS.  Women aged between 18-40 years of age were assigned to receive a placebo or 220 mg zinc sulphate (50mg elemental zinc) for 8 weeks.  All participants were administered metformin (300mg increased to 1500mg by week 3 to monitor side effects).

After 8 weeks, 41% of women saw an improvement in their hair compared to 12% of women in the placebo group. Women in the placebo group also saw a reduction in excess body hair, with around 75% reporting favourable results compared to around 20% of women in the placebo group.  The results of the study indicated that taking 50 mg elemental zinc for 8 weeks among women with PCOS had beneficial effects on hair loss and excess body hair: however [8].

Several trials conducted worldwide support the use of zinc supplementation for hair loss.  Depending on baseline levels zinc supplementation may be required for 12-18 months, with early results expected after 16 weeks for moderate to severe hair loss conditions.  Mild cases of hair loss may see improvement earlier.

THE FINAL WORD

Hair loss due to PCOS can be reversed if the underlying hormonal imbalance is corrected.  Once PCOS is diagnosed with blood tests or with an ultrasound, treatment may help with symptoms.

Blood tests may also reveal other medical issues such as low thyroid function or vitamin and mineral deficiencies contribute to the severity of PCOS symptoms.  Zinc supplementation can support hair regrowth and control excess body hair by managing the production of DHT.

Evidence supports positive PCOS management by lifestyle changes that are aimed at reducing metabolic abnormalities with or without the use of insulin sensitising drugs, especially with woman with PCOS and normal insulin sensitivity.

Increasing levels of physical activity and reducing intake of starchy carbohydrates and sugary foods help to reduce insulin levels and reduce the severity of PCOS symptoms.

If you are experiencing hair loss and you have PCOS, talking to your doctor can help give you more clarity on the options available to you.  Hair regrowth is certainly possible with the right guidance and advice.

REFERENCES

  1. Why visceral fat is bad: mechanisms of the metabolic syndrome. Obesity14(2S), p.16S.
  2. Ketogenic diet in women with polycystic ovary syndrome and liver dysfunction who are obese: A randomized, open‐label, parallel‐group, controlled pilot trial. Journal of Obstetrics and Gynaecology Research47(3), pp.1145-1152.
  3. Exploring the relationship between gut microbiota and exercise: short-chain fatty acids and their role in metabolism. BMJ open sport & exercise medicine7(2), p.e000930
  4. Association of anemia with serum sex hormone binding globulin levels in patients with polycystic ovary syndrome. PAFMJ70(6), pp.1870-73.
  5. Association of High Levels of Testosterone and Ferritin with Overweight in Women with PCOS. Journal of Fasa University of Medical Sciences11(2), pp.3886-3894.
  6. Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids77(4), pp.300-305.
  7. Steroid-binding specificity of human sex hormone-binding globulin is influenced by occupancy of a zinc-binding site. Journal of Biological Chemistry275(34), pp.25920-25925.
  8. Effects of zinc supplementation on endocrine outcomes in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Biological trace element research170(2), pp.271-278.