Obesity, not always, but often, an accompanying problem, worsens the presentation of PCOS. Current treatment guidelines for PCO, therefore, strongly recommend ‘weight management’ (both weight loss and the prevention of excess weight gain) through diet and exercise as an initial treatment strategy.
But how effective are these ‘lifestyle’ strategies and how consistent are the improvements?
This was the topic of a recent review by Lisa Moran and colleagues from Australia, published in the Cochrane Database of Systematic Reviews.
The authors identified six randomised controlled trial (including a total of 165 participants). Three studies compared physical activity to minimal dietary and behavioural advice or no advice; three compared combined dietary, exercise and behavioural interventions to minimal intervention.
Although these interventions resulted in modest weigh loss (~3.5 kg) and significantly reduced testosterone levels and associated male-pattern hair growth (hrisutism) as well as fasting insulin levels, there was no relevant effect on glucose or lipid levels or other cardiovascular risk factors.
Notably, none of these studies examined the impact of these interventions on quality of life, patient satisfaction or reproductive health (a common problem in PCOS). There was also no assessment of depression or anxiety, which have been reported to be commonly associated with PCOS.
Perhaps, as the authors point out, the most important result of this analysis is the apparent paucity of large studies that have addressed this issue – surprising enough, given that as many as 1 in 5 women of reproductive age may present with this problem and PCOS is a major cause of female infertility.
As the authors note:
“This review has identified that there are limited well-designed studies in lifestyle intervention in PCOS that are available to guide clinical practice.”
Given the impact of PCOS on reproductive health, it is most surprising that
“There are no existing RCT data identified in this review to assess whether lifestyle intervention improves reproductive outcomes including fertility, menstrual regularity or ovulation”
The overall conclusion is thus rather sobering:
“With the current evidence, it is not possible to comment on the relative effectiveness or sustainability of different durations or types of lifestyle interventions, or their relative success, in a weight loss or non-weight loss environment or with overweight or non-overweight participants……this indicates a considerable gap in the research literature.”
On other hand, this paucity of data should not be interpreted to show that interventions aimed at weight management do not impact on fertility or reproductive health in overweight and obese women with PCOS. Indeed, there is now accumulating anecdotal evidence that more significant weight loss (as can be achieved with bariatric surgery) may prove most beneficial in women with PCOS both in terms of reducing symptoms as well as in improving chances of conception.
Still, one wonders why a topic of such importance has not received more attention from researchers or funding agencies.
New York, NY
Moran LJ, Hutchison SK, Norman RJ, & Teede HJ (2011). Lifestyle changes in women with polycystic ovary syndrome. Cochrane database of systematic reviews (Online) (2) PMID: 21328294
Although the exact etiology of PCOS remains unclear, it is commonly associated with overweight and obesity, with patients often (but not always!) presenting with signs of increased androgen production (or action) and (often quite severe) insulin resistance.
Clinically the signs and symptoms of PCOS can range from mild menstrual disorders to severe disturbance of reproductive and metabolic functions.
Because of its variability, the definition of PCOS has changed over the years – current diagnoses requires the demonstration of hyperandrogenism and ovarian dysfunction (including infrequent or irregular ovulation or anovulation) and/or polycystic ovaries as demonstrated by imaging (e.g. ultrasound).
A paper by Ahmed Badawy and Abubaker Elnashar from the Universities of Mansoura and Benha, Egypt, just published in the International Journal of Women’s Health, presents a comprehensive overview of the current treatment options for PCOS.
With regard to excess weight, the authors note:
Obesity is observed in 35%–60% of women with PCOS and is related to lack of or delayed response to different treatments…Weight loss improves the endocrine profile and increases the likelihood of ovulation and pregnancy. Normalization of the menstrual cycles and ovulation could occur with modest weight loss as little as 5% of the initial weight. Weight loss can improve not only circulating androgen and glucose levels but also ovulation and pregnancy rates in obese women with PCOS.
The authors also report that a few recent studies describe high success rates in restoring regular cycles and pregnancies in severely obese women with PCOS, who underwent bariatric surgery.
The paper describes in great detail other treatment options that can often complement weight loss, including the use of medications such as clomiphene citrate, tamoxifen, aromatase inhibitors, metformin, glucocorticoids, or gonadotropins or even surgically by laparoscopic ovarian drilling.
Treatment options of course also include in vitro fertilization as a last resort to achieve pregnancy when all other treatments fail.
The paper also touches on the treatment of androgenic symptoms, such as excessive hair growth on the body and face, balding, or acne.
Given that PCOS is such a common problem, I wonder if my readers wish to share their experience with managing this syndrome.
As always, comments are greatly appreciated.
Badawy A, & Elnashar A (2011). Treatment options for polycystic ovary syndrome. International journal of women’s health, 3, 25-35 PMID: 21339935
But how exactly can excess body weight affect reproductive function in women?
A possible explanation comes from a study by Natalia Igosheva and colleagues from King’s College London, London, UK, just published in PLoS.
Using an established mouse model of maternal diet-induced obesity and live cell dynamic fluorescence imaging techniques, the researchers demonstrated that maternal obesity prior to conception is associated with altered mitochondria in mouse oocytes (eggs) and zygotes.
Specifically, maternal diet-induced obesity in mice led to an increase in mitochondrial potential, mitochondrial DNA content and biogenesis. Generation of reactive oxygen species (ROS) was raised while glutathione was depleted and the redox state became more oxidised, suggestive of oxidative stress. (for my non-technical readers, it suffices to say that none of this is good for the egg or the zygote).
These altered mitochondrial properties were associated with significant developmental impairment as shown by the increased number of obese mothers who failed to support blastocyst formation compared to lean dams.
These studies show that compromised oocyte and early embryo mitochondrial metabolism, resulting from excessive nutrient exposure prior to and during conception, may underlie poor reproductive outcomes frequently reported in obese women.
While the leap from mice to women may seem a bit of a stretch, there is no doubt that in many overweight and obese women trying to become pregnant, weight loss is clearly one of the most effective strategies.
Now all we need are more effective strategies to help manage excess weight.
Igosheva N, Abramov AY, Poston L, Eckert JJ, Fleming TP, Duchen MR, & McConnell J (2010). Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes. PloS one, 5 (4) PMID: 20404917
Yesterday, on my way to the American Heart Association Meeting in Orlando, I read Malcolm Gladwell’s recently published anthology of articles he wrote for The New Yorker magazine, now published under the name, “What the Dog Saw”.
Of all the fascinating essays, the one that I found most interesting in terms of its implications for women’s health, was the story of the discovery of the birth-control pill and how it has led to a complete transformation of women’s societal role and health.
The essay starts with the story of John Rock, a devout Catholic and one of the inventors of the pill. For most of his life Rock tried (unsuccessfully) to harness acceptance for his invention by his Church as a “natural” method of birth control. The Church, however, failed to follow his argument that the pill should be considered a “natural” method, because it essentially uses a “natural” hormone (progesterone) to simply mimic a “natural” state of pregnancy and thereby prevent ovulation.
Apparently, it was also to further support his argument of “normalcy”, that Rock and his collaborator Gregory Pincus devised the idea of introducing a monthly interruption in hormone delivery to trigger monthly menstrual periods. The underlying assumption for the latter was that monthly periods were indeed “normal” for women of reproductive age.
The interesting twist in Gladwell’s essay, however, comes when he goes on to describe how throughout most of human history, women did not actually have monthly periods through most of their reproductive years.
As an example for this Gladwell cites the work by Beverly Strassmann, who studied menstrual periods amongst women in the Dogon tribe of Mali. Not only did the Dogon women on average experience their first periods at age 16, but in addition they spent so much time either pregnant or breast feeding that they generally experienced only around a 100 periods over their lifespan.
This situation is of course fundamentally different from women in Western societies today, who not only have their first periods at age 12 (in part due to increasing adiposity?), but as a result of delayed and fewer pregnancies as well as markedly shorter breast feeding, experience almost 400 periods over their lifetime.
Each menses not only involves ovulation, growth and sloughing of the endometrium, but also increased cellular division of the breast. Gladwell cites work by Malcolm Pike and others, who argue that this remarkable increase in the number of menstrual cycles explains virtually all of the excess risk for ovarian, endometrial and breast cancer seen in “Western” women.
Thus, avoiding menstrual cycles (or rather pushing these back to around 100 over a lifetime) may be a major strategy to reduce the incidence of these cancers. While giving the birth-control pill over longer time intervals (rather than just for 3 weeks at a time) may work to reduce the frequency of menses to say 4-times a year and thereby reduce the risk of ovarian and endometrial cancer, the fact that the pill still contains some estrogen may actually not do much for breast cancer. Pike and colleagues therefore apparently suggest using GnRH (gonadotropin-releasing hormone) antagonists, thereby mimicking menopause rather than pregnancy.
While, I can only assume that this concept still remains fairly controversial, if true, it certainly bears some significance for young girls, especially those with excess weight.
Readers of these pages are probably well aware that overweight girls often get their first periods significantly earlier than normal-weight girls. In addition, overweight girls may also be more reluctant to take the pill due to fear of adverse effects (hypertension, thombosis, etc.).
What if, as discussed by Gladwell, early menarche and late (as well as fewer) pregnancies truly is a major risk factor for female reproductive cancers?
What if much of this is further exacerbated by excess weight (earlier menarche, fewer pregnancies and higher estrogen levels)?
While most readers will perhaps think oral contraception acceptable for a 16 year-old, most of us would probably find any suggestion of starting a 10-year old on pills to suppress menstrual cycles rather disturbing.
I am certainly not a reproductive endocrinologist or oncologist, nor do I pretend to know much of the literature on this, but the Gladwell essay certainly got me thinking.
As always, all comments are very much appreciated.
This may be an interesting consequence of the obesity epidemic, based on new research by Sarah Keim and colleagues from the National Institute of Child Health and Human Development, Bethesda, MD, USA, just published in EPIDEMIOLOGY.
In a follow-up study of the prospective Collaborative Perinatal Project, about 600 grown daughters were asked in 1987-1991 for their age at menarche and compared to data from the original Collaborative Perinatal Project (1959-1966), which included their mothers’ height and prepregnancy weight.
Compared with mothers with a BMI less than 25, the daughters of mothers with a BMI of 30 or greater were three times more likely to experience their first period at ages 12 or younger. This association remained after adjusting for maternal age at menarche, maternal parity, socioeconomic status, and other factors.
While the data clearly show an association between maternal obesity and younger menarcheal age among daughters in this study, the study of course does not prove causality nor does it provide any insight into the biological mechanisms underlying this association.
Nevertheless, I do wonder about the consequences of early menarche on the psyche and physical development of young girls born to obese mothers and its impact on future generations.