The following is a summary of the findings from research projects conducted in the UCLH family of hospitals from 2006 to 2014 by Paul Hardiman and associated researchers. Note that other studies will be added to this list in the near future.
|Relaxation therapy improves biochemical levels and mood in women with polycystic ovary syndrome
Elevated testosterone is one of the diagnostic features of PCOS. Some of this testosterone is a by product of biochemicals (such as DHEAS and androstenedione) being produced by the adrenal glands. In theory, reduction of adrenal activity will reduce production of these biochemicals. To test this hypothesis, 13 women with PCOS underwent six weekly treatment sessions, and a follow-up session, of calming breathing, muscle relaxation, and guided imagery. The main outcome measures were mood and quality of life (QoL) - assessed using validated questionnaires - and hormones, which were measured in blood samples with the gold-standard technique (mass spectrometry). We found small but statistically significant reductions in adrenal biochemicals, including cortisol, though not testosterone, and statistically significant improvments in anxiety and depression, but not QoL. This is the first study to use a relaxation program to reduce adrenal androgens in PCOS and has potentially useful clinical applications in the treatment of PCOS.
Barry, J. A., Leite, N., Sivarajah, N., Keevil, B., Owen, L., Miranda, L., Qu, F., & Hardiman, P. J. (2017). Relaxation and Guided Imagery Significantly Reduces Androgen Levels and Distress in Polycystic Ovary Syndrome: Pilot Study. Contemporary Hypnosis & Integrative Therapy, 31
Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis
We conducted a systematic review and meta-analysis of all cancer studies up to Oct 2013 which included women with PCOS. Studies were reviewed if they compared women with PCOS to non-PCOS groups for fatal or non-fatal gynaecological cancers. From 698 references, 11 studies (5 of endometrial cancer and 3 each of ovarian and breast cancer) met the inclusion criteria. Although the risk of ovarian and breast cancer was not significantly increased in women with PCOS of any age, we found that women with PCOS under the age of 54 years old were at roughly double the risk of ovarian cancer and roughly four times the risk of endometrial cancer compared to other women. However, we would like to emphasise the fact that although these findings are based on the best studies available, these studies in some cases are far from ideal (e.g. PCOS was not always diagnosed in the same way across studies) and this may have exaggerated the risk to women with PCOS. Furthermore, women who have PCOS should be aware that any increased risk for endometrial cancer must be judged in the context of its relatively low incidence in the general population. We conclude that what is needed is a large well-controlled prospective study in order to gain a more accurate estimate of the risk of gynaecological cancers in women with PCOS.
Barry, J. A., Azizia, M. M., & Hardiman, P. J. (2014). Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. Human reproduction update, 20(5), 748-758.
Risk of coronary heart disease and risk of stroke in women with polycystic ovary syndrome: A systematic review and meta-analysis
We conducted a systematic review and meta-analysis of all studies of coronary heart disease and stroke published up to Oct 2011 which included women with PCOS. In studies where where the average age was more than 45 years old, the risk of non-fatal coronary heart disease was somewhat higher (though non-signficantly; p<.09) in PCOS, but the risk in for non-fatal stroke was almost double in PCOS (p<.008). The authors suggest that clinicians and policymakers might focus on screening women with PCOS as soon as it is diagnosed, and focus on applying preventative measures, such as lifestyle interventions, appropriate to reducing the risk of stroke.
Anderson, S. A., Barry, J. A., & Hardiman, P. J. (2014). Risk of coronary heart disease and risk of stroke in women with polycystic ovary syndrome: A systematic review and meta-analysis. International journal of cardiology, 176(2), 486-487.
Is depression overestimated in PCOS?
The authors caution researchers against unwittingly over-emphasising the degree of depression in women with PCOS. The evidence fromthe meta-analysis by Barry et al (2011) suggests that women with PCOS are at risk of mild levels of depression, but some researchers fail to report clearly the clinical significance of their findings e.g. one study stated in their abstract that 67% of women with PCOS were found to be depressed, but did not state until much later in the paper that almost half of these had only mild depression. While it is important to recognise psychological aspects of PCOS, it is equally important to recognise them accurately.
Barry, J. A., Kuczmierczyk, A. R., & Hardiman, P. J. (2014). Reporting the Rates of Depression in Polycystic Ovary Syndrome (PCOS). The journal of sexual medicine, 11(7), 1882-1883.
Cognitive advantage due to testosterone in women with PCOS
Polycystic ovary syndrome (PCOS) is a condition characterised by elevated testosterone levels. Some research in healthy men and women has found that 3-dimensional (3D) mental rotation ability
is positively correlated with testosterone levels. Our study of 69 women with PCOS and 41 women without PCOS found that women with PCOS who had elevated testosterone levels scored
significantly higher than the other women (p<.047).
Within the PCOS group, testosterone was significantly positively correlated with 3D scoring (p < .002), whereas estrogen was significantly negatively correlated with 3D scoring (p < .010).
Barry, J. A., Parekh, H. S. K., & Hardiman, P. J. (2013). Visual-spatial cognition in women with polycystic ovarian syndrome: the role of androgens. Human reproduction, det335.
Signs of cardiovascular risk in PCOS
Polycystic ovary syndrome (PCOS) is associated with endothelial dysfunction, which may be caused by elevated levels of asymmetric dimethylarginine (ADMA). ADMA reduces nitric oxide production in diabetes mellitus, hypertension and renal failure. Symmetric dimethylarginine (SDMA) is a stereoisomer produced alongside
ADMA, and has recently been described as a risk factor for cardiovascular events. In this cross-sectional study based in a teaching hospital, 16 women with PCOS were recruited alongside
15 healthy controls, and fasting venous blood samples were obtained. Renal function was measured, and ADMA and SDMA were analysed using a high-performance liquid chromatography method. After controlling for BMI, mean ADMA and SDMA levels in women
with PCOS were higher than in controls (p = 0.036 and p = 0.030, respectively). Renal function was not different between the two groups (p = 0.152). Women with PCOS have raised levels of SDMA,
a molecule implicated in endothelial dysfunction and long-term cardiovascular risk.
Lakhani K, Kay AR, Leiper J, Barry JA, Hardiman PJ. (2011).
Symmetric dimethylarginine (SDMA) is raised in women with polycystic ovary syndrome: a pilot study. Journal of Obstetrics & Gynaecology, 31, 5, 417-419
Eating behaviour and psychological symptoms typical of low blood sugar
The idea that diet can affect mood and behaviour in women with polycystic ovary syndrome (PCOS) by altering blood glucose levels has become popular in recent years. This paper describes an online survey (N = 462) of 24 women with PCOS, 299 healthy control women, 47 women who possibly had undiagnosed PCOS, and 92
men. The groups were compared for symptoms of mood and behavioural symptoms typical of reactive (postprandial) hypoglycemia. The outcome measures were two questionnaires
that measure states associated with hypoglycemia:
the Hypoglycemia Symptom Checklist-7 (HSC-7), which measures behavioural symptoms and the Mood Adjective Checklist (MACL), which measures emotional states. Controlling for age and body
mass index (BMI) using between-groups analysis of covariance (ANCOVA), the women with PCOS scored significantly higher than
the other three groups (p < 0.001) on the outcome measures.
These differences remained statistically significant in a subset of twelve women with PCOS compared to twelve healthy control women closely matched for age, BMI, and eating behaviour. The findings are suggestive of hypoglycemia-related mood and behavioural problems in PCOS. Future research should test whether blood glucose levels correlate with these symptoms in PCOS, and whether a low glycemic index (‘low-GI’) diet improves the symptoms.
Barry JA, Bouloux P, Hardiman, PJ (2011). The impact of eating behavior on psychological symptoms typical of reactive hypoglycemia: a pilot study comparing women with polycystic ovary syndrome to controls. Appetite, 57, 73-76
Testosterone and mood in PCOS
Women with polycystic ovarian syndrome (PCOS) have been found
to suffer from fertility problems and mood dysfunction. To control
for any effect of fertility problems, the present study compared
mood dysfunction in women with PCOS to non-PCOS women with fertility problems. Seventy-six women with PCOS and 49 subfertile controls reported their anxiety, depression and aggression levels,
and the relationship between mood and testosterone (T) was assessed. Controlling for age and BMI using MANCOVA, women
with PCOS were significantly more neurotic (had difficulty coping
with stress) than controls, had more anger symptoms, were significantly more likely to withhold feelings of anger and had more quality of life problems related to the symptoms of their condition (acne, hirsutism, menstrual problems and emotions). In a subgroup of 30 women matched on age, BMI and ethnicity, it was found that women with PCOS were significantly more anxious and depressed than controls.
T was not generally correlated with mood states. This is the first study to identify problems with neuroticism and withholding anger
in women with PCOS. These mood problems appear to be mainly attributable to PCOS symptoms, though other factors, such as hypoglycaemia, cannot be ruled out.
Barry JA, PJ Hardiman, BK Saxby, A Kuczmierczyk (2011). Testosterone and Mood Dysfunction in Women With Polycystic Ovarian Syndrome Compared to Subfertile Controls. Journal of Psychosomatic Obstetrics and Gynecology, 32, 2, 104-11
Testosterone levels in the umbilical cord
The aetiology of polycystic ovary syndrome (PCOS) is poorly understood, but an intrauterine hyperandrogenic environment
has been implicated. This study was designed to assess whether
the female offspring of mothers with PCOS are exposed to raised levels of testosterone (T) in utero. In this case–control study,
three groups of pregnant women were recruited from the labour
ward: PCOS women with a female baby (n = 10, PCOS girls); control women with a female baby (n = 20, control girls) and control women with a male baby (n = 10, control boys). Maternal and umbilical vein (UV) blood was assayed for T levels. UV T in PCOS girls was significantly raised, compared with control girls (p < 0.012). The difference in UV T between PCOS girls and control boys was not significant (p < 0.254). This is the first demonstration of a hyperandrogenic in utero environment in PCOS pregnancies; UV T in female infants is raised to male levels.
Barry JA, Kay AR, Navaratnarajah R, Iqbal S, David AL, Bamfo JEAK, Hines M, Hardiman PJ. (2010). Umbilical vein testosterone in female infants born to mothers with Polycystic Ovary Syndrome is elevated to male levels. Journal of Obstetrics & Gynaecology, 30, 5, 444-6.
Anxiety and depression in women with PCOS
In a review of 12 previously published studies, it was found that women with PCOS on average tend to experience slightly elevated anxiety and depression compared to women without PCOS. These levels were reduced a little - but not completely - when obesity was taken into account.
Barry JA, Kuczmierczyk AR, Hardiman PJ (2011). Anxiety and depression in polycystic ovary syndrome: a systematic review and meta-analysis. Human Reproduction. 26, 9, 2442-51
Here is a further election of research that may be of interest to women with PCOS. Note that this list isn't meant to be exhaustive, and many more extremely good research papers exist. Interested readers are advised to do a keyword search of the excellent PubMed database (go to http://www.ncbi.nlm.nih.gov/pubmed).
Abbott DH, Zhou R, Bird IM, Dumesic DA, Conley AJ. Fetal programming of adrenal androgen excess: lessons from a nonhuman primate model of polycystic ovary syndrome. Endocr Dev. 2008;13:145-58.
Bhatia V. Insulin resistance in polycystic ovarian disease. South Med J. 2005 Sep;98(9):903-10; quiz 911-2, 923.
Chittenden BG, Fullerton G, Maheshwari A, Bhattacharya S. Polycystic ovary syndrome and the risk of gynaecological cancer: a systematic review. Reprod Biomed Online. 2009 Sep;19(3):398-405.
de Groot PC, Dekkers OM, Romijn JA, Dieben SW, Helmerhorst FM. PCOS, coronary heart disease, stroke and the influence of obesity: a systematic review and meta-analysis. Hum Reprod Update. 2011 Jul-Aug;17(4):495-500.
Dumesic DA, Abbott DH, Padmanabhan V. Polycystic ovary syndrome and its developmental origins. Rev Endocr Metab Disord. 2007 Jun;8(2):127-41.
Farrell K, Antoni MH. Insulin resistance, obesity, inflammation, and depression in polycystic ovary syndrome: biobehavioral mechanisms and interventions. Fertil Steril. 2010 Oct;94(5):1565-74. Epub 2010 May 14.
Himelein MJ, Thatcher SS. Polycystic ovary syndrome and mental health: A review. Obstet Gynecol Surv. 2006 Nov;61(11):723-32.
Raja-Khan N, Stener-Victorin E, Wu X, Legro RS. The physiological basis of complementary and alternative medicines for polycystic ovary syndrome. Am J Physiol Endocrinol Metab. 2011 Jul;301(1):E1-E10.
Månsson M, Norström K, Holte J, Landin-Wilhelmsen K, Dahlgren E, Landén M. Sexuality and psychological wellbeing in women with polycystic ovary syndrome compared with healthy controls. Eur J Obstet Gynecol Reprod Biol. 2011 Apr;155(2):161-5. Epub 2011 Jan 12.