Women’s lifestyle and sexual function
Karsten, Matty
DOI:
10.33612/diss.125792427
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date: 2020
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Karsten, M. (2020). Women’s lifestyle and sexual function: the effects of a preconception intervention in women with obesity. University of Groningen. https://doi.org/10.33612/diss.125792427
Copyright
Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.
WOMEN’S
LIFESTYLE and
SEXUAL FUNCTION
the effects of a preconception
intervention in women with obesity
Women’s Lifestyle and Sexual Function
the effects of a preconception intervention in women with obesity
PhD thesis, University of Groningen, with a summary in English and a summary in Dutch. Copyright © by M.D.A. (Matty) Karsten
All rights reserved. No part of this (electronic) thesis may be reproduced, stored in a retrieval system or transmitted in any form or by any means without prior permission of the copyright owner and the publisher holding respective copyrights of the published articles, if applicable.
Author: M.D.A. Karsten
Cover design: James Jardine, www.jamesjardine.nl
Layout: James Jardine, www.jamesjardine.nl
Photography: Stephan Keereweer, www.stephankeereweer.nl Printing: Ridderprint BV, www.ridderprint.nl
ISBN (printed thesis): 978-94-034-2508-5 ISBN (electronic thesis): 978-94-034-2507-8 The research described in this thesis was supported by:
A grant of the Dutch Heart Foundation (2013T085), a grant from the European Union’s Horizon 2020 research and innovation program DynaHealth (633595) and ZonMw (50-50110-96-518).
Printing of this thesis was supported by:
The Graduate School of Medical Sciences, Research Institute SHARE, University of Groningen, University Medical Center Groningen, the Department of Clinical Epidemiology, Biostatistics and Bioinformatics of the Amsterdam UMC, Amsterdam Reproduction & Development (AR&D) research institute, Chipsoft, Goodlife, Ferring B.V. and Moeders voor Moeders.
Financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged.
The digital version of this thesis can be found online at: https://www.publicatie-online.nl/publicaties/m-karsten Or by scanning the QR code
the effects of a preconception intervention in women with obesity
Proefschrift
Ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen
op gezag van de
rector magnificus prof. dr. C. Wijmenga en volgens besluit van het College voor Promoties.
De openbare verdediging zal plaatsvinden op woensdag 10 juni om 16:15 uur
door
Mathilde Danitsja Adaja Karsten
geboren op 18 januari 1989 te Almere
Prof. dr. A. Hoek Prof. dr. T.J. Roseboom Copromotor Dr. H. Groen Beoordelingscommissie Prof. dr. P. Enzlin
Prof. dr. E.F.C. van Rossum Prof. dr. ir. D. Kromhout
Dr. V. Wekker N. Toussaint, PhD
PART I WOMEN’S LIFESTYLE
Chapter 2 Effects of a preconception lifestyle intervention in obese infertile women on diet and physical activity; a secondary analysis of a randomized controlled trial
PLoS ONE 2018 Nov; 13(11):e0206888
33
Chapter 3 Determinants of successful lifestyle change during a 6-month preconception lifestyle intervention in women with obesity and infertility
European Journal of Nutrition 2018 Sep; 58(6):2463-2475
57
Chapter 4 Preconception lifestyle intervention reduces long term energy intake in women with obesity and infertility: a randomised controlled trial
International Journal of Behavioral Nutrition and Physical Activity 2019 Feb; 16(1):3
93
PART II WOMEN’S SEXUAL FUNCTION
Chapter 5 A lifestyle intervention improves sexual function of women with obesity and infertility: a 5 year follow-up of a RCT
PloS ONE 2018 Oct; 13(10):e0205934
119
Chapter 6 The role of PCOS in mental health and sexual function in women with obesity and a history of infertility
Submitted
141
Chapter 7 Sexual function and pelvic floor activity in women: the role of traumatic events and PTSD symptoms
Submitted
163
PART III APPENDICES
English Summary 203
Dutch Summary (Nederlandse Samenvatting) 207
List of Contributing Authors 211
PhD Portfolio 215
List of Publications 219
Research Institute SHARE 221
Acknowledgements (Dankwoord) 225
About the Author (Over de Auteur) 247
CHAPTER 1
General Introduction
1
This dissertation consists of two parts: the first part is focussing on women’s lifestyle and the second part on women’s sexual function.
P A R T I – W O M E N ’ S L I F E S T Y L E
Overweight and obesity: worldwide trend and causes
Overweight and obesity are increasingly prevalent and lead to chronic non-communicable diseases around the globe.1 To date, nearly one third of the world’s population is either
overweight or obese.2 Overweight in Western societies is typically defined as a BMI (weight
divided by height squared) of 25 to 30 and obesity is defined as a BMI of 30 or higher.3
The prevalence of overweight and obesity is generally higher in women than in men.2 The mean
BMI of women is shown in Figure 1.1.4 Although the Netherlands has lower rates of overweight
or obesity than other European countries and the United States5, the rates are alarmingly high.6
With nearly one in three women of reproductive age being overweight (24.6% in women aged 20 to 29 years and 30.1% in women aged 30 to 39 years in 2018) or obese (7.9% in women aged 20 to 29 and 13.7% in women aged 30 to 39 in 2018).6
Causes of overweight and obesity
Overweight and obesity are the consequence of a positive energy balance between the intake of calories and calories expended, leading to an excess of energy that is stored in in adipose tissue.7 The cause of overweight and obesity is multifactorial, the interaction of several genetic,
behavioural, socioeconomic and environmental factors attribute to their development.8 Global
economic growth has led to rapid changes in the environment due to: increased portion sizes, intake of energy-dense foods and a decrease in physical activity due to sedentary lifestyles in terms of work, modes of transportation and increasing urbanisation1, which led to the so called
‘obesogenic environment’.9 The obesogenic environment has been defined as the ‘sum of
influences that the surroundings, opportunities, or conditions of life have on promoting obesity in individuals or populations’.9
Excess adiposity is not only linked with an increased body size, but also leads to metabolic consequences.10 Overweight and obesity increase the risk of many non-communicable
diseases such as cardiometabolic diseases, type II diabetes mellitus,1,11 some forms of cancer12,
and mental health problems such as depression.13 In women of reproductive age obesity leads
to longer time to pregnancy14,15, higher chances of infertility14,16 and an increased risk for
pregnancy complications17,18. The offspring of obese mothers have a higher risk of becoming
obese themselves19–21, with higher blood pressures22, an increased risk of cardio metabolic
1 1975 2014
18.5 25 30 35 kg/m2
FFiigguurree 11..11.. Age-standardised mean BMI in women by country from 1975 to 2014
Adapted from: NCD Risk Factor Collaboration. Lancet. 2016; 387(10026):1377-1396. 4
Figure 1.1. Age-standardised mean BMI in women by country from 1975 to 2014
Adapted from: NCD Risk Factor Collaboration. Lancet. 2016; 387(10026):1377-1396. 4
Lifestyle change as first step in the treatment of overweight and obesity
Improving lifestyle, through a healthy diet and increasing physical activity is recommended as a first step in treatment of overweight and obesity.25–27
Dietary intake and Physical activity
Both dietary intake and physical activity are daily recurring lifestyle behaviours as part of our inherent physiological humans needs. Dietary intake refers to an individual’s daily eating pattern, including the number of calories, the specific foods and beverages and the relative quantities consumed28. Physical activity includes all bodily movements produced by our
skeletal muscles that require energy expenditure29, including bodily movements performed
while working, playing, active transportation, and during household- and recreational activities. Exercise is not the same as physical activity, but can be considered as the part of physical activity that is planned, structured, repetitive and is done with a certain purpose (e.g. to maintain a certain level of fitness).29
Both reducing dietary intake and increasing physical activity can contribute to weight loss if more energy is expended than consumed, resulting in a negative energy balance. These changes in lifestyle, however, require behaviour change, which is often very difficult30–33 since
lifestyle behaviours are intertwined with many aspects of our daily living and involve a high percentage habitual actions31,34,35. Most lifestyle interventions often result in modest short term
1
term lifestyle changes35,39,40. A systematic review showed that, in most studies, dietary changes
returned to baseline after 12 months of follow-up unless the intervention program remained highly intensive.41
Since lifestyle change is difficult, not all individuals participating in a lifestyle intervention programs will achieve the intended goal38,42,43, and 10 to 80% of all participants will not
complete the intervention at all, depending on duration and intensity of the program.44,45 It
is unclear which factors relate to successful lifestyle change, to date, insufficient research attention has been paid to the aspects that determine whether someone succeeds in changing lifestyle.46,47 Studies have investigated psychological and behavioural factors, such as
self-efficacy, goal setting, social support and motivation43,48 as determinants of lifestyle change.
In a review, the most consistent determinants of lifestyle change were: a higher autonomous self-motivation, a high self-efficacy level and self-regulation skills (such as self-monitoring).48
Identifying determinants of a successful lifestyle change in participants of lifestyle intervention programs will provide tools to improve interventions for women with overweight, obesity or an unhealthy lifestyle. If we know the determinants of success, it will be possible to personalise interventions and increase effectiveness of interventions. In chapter 3 of this dissertation we therefore aimed to identify biopsychosocial determinants of successful lifestyle change and program completion of a preconception lifestyle intervention in women with obesity.
Intervening during the preconception period
Although changing and maintaining lifestyle is difficult, the period before and during pregnancy may be an optimal period in which women are receptive to dietary and lifestyle advice, and can therefore be seen as a an optimal time window to intervene.49,50 During this time period,
besides their own health, women also feel responsible for the health of their child.50 Intervening
in the preconception period may benefit both the woman and her future child. Moreover, interventions in smoking- and alcohol cessation for example, are therefore particularly successful in pregnant women or women with a wish to conceive.49,51,52 In chapter 2 and 4 of
this dissertation, we therefore aimed to investigate the immediate short-term and sustainable long-term effects of a preconception lifestyle intervention on women’s dietary intake and physical activity patterns.
P A R T I I – W O M E N ’ S S E X U A L F U N C T I O N
Sexual function
Sexual function is the way in which the body and mind respond to sexual stimulation and the various stages of sexual response.53 These stages can be seen in the Human Sexual Response
Cycle (Figure 1.2).54 Female sexual dysfunction refers to an impaired ‘ability to respond
sexually or to experience sexual pleasure’55 and can take different forms of impairment to
the stages of sexual response, such as a decreased sexual interest, desire or arousal, the inability to achieve orgasm, genito-pelvic pain during sexual activity, penetration disorder, substance or medication-induced sexual dysfunction, a decreased sexual satisfaction, or a combination of these problems (Diagnostic and Statistical Manual of Mental Disorders (DSM), 5th Edition55). Generally, more sexual dysfunctions are reported in women than in men in
the few studies that include both sexes56, noting that fewer studies have been performed in
women.56,57 Female sexual function can be understood through a biopsychosocial model,
which is biologically driven, but is experienced through a complex interplay between (neuro) biological, sociocultural, psychological- and interpersonal factors.55,58,59
Sexual function and obesity
Sexual function seems decreased in women with obesity60 compared to normal weight
women61,62 and weight loss can improve sexual function.63,64 The association between obesity
and sexual function in women is complex, at least three different pathways can explain their relationship: direct effects from excess adipose tissue, co-occurring pathophysiological conditions and mediating effects of psychological factors.65 Pathophysiologic comorbidities of
obesity such as metabolic syndrome66,67, dysregulation of oestrogen and androgen levels68,
and a poorer endothelial function that is important for vaginal lubrication69–71, can all have a
negative effect on sexual function in women with obesity. Moreover, women with obesity are more often dissatisfied with their body, and this can lower sexual desire and arousal.72,73
There is some evidence that weight loss increases female sexual function56,65, especially in
women who had been diagnosed with sexual dysfunction prior to the start of the intervention.74,75
In chapter 5 of this dissertation, we therefore aimed to study the effects of a lifestyle intervention on women’s sexual function.
1
Figure 1.2. Human Sexual Response Cycle.
Once sexual desire is accessed, receptivity to sexual stimuli increases, and proceeding of these stimuli in the mind is more likely to lead to further and more intensive arousal.
Adapted from: R. Basson. Journal of Sex & Marital Therapy, 2001;27(1):33-43. 54
Mental health and sexual function
Mental health and sexual dysfunction are intertwined, as mental health problems can be seen as the most important risk factor for sexual dysfunction76, even to a higher extent than physical
function.76,77 Depression is linked to a low sexual desire78, sexual arousal and sexual pleasure 79 and sexual dysfunction in general.80 A negative mood, apart from depression, has also
been linked to a decreased sexual function.80 Furthermore, anxiety has been linked to a lack
of subjective arousal76, pleasure and orgasm.81 In anxiety the physical sensations of sexual
arousal can get neurologically linked to fear rather than pleasure.82,83 Medications such as
antidepressants wherein the reuptake of serotonin is blocked resulting in receptor inactivity84,85,
can induce sexual dysfunction leading to a suppression of sexual desire and a delay or absence of orgasm through inhibiting dopamine signalling in brain circuits.84–86 Furthermore, traumatic
experiences83,87–89, relationship difficulties90–93 and stigmatisation94–96 as social aspects of
mental health can also contribute to a decreased sexual functioning.
Traumatic events and Post-Traumatic Stress Disorder
Worldwide, it is estimated that 70% of men and women experience at least one traumatic event during their lifetime.97 Although most recover, a minority suffers from enduring severe
psychological and emotional distress resulting in post-traumatic stress disorder (PTSD).98 The
gender and trauma type.99 Women are more likely to develop PTSD than men, when exposed
to the same kinds of trauma.100 Furthermore, individuals with interpersonal traumas have the
highest risk of developing PTSD, especially following exposure to rape and sexual assault (19% and 11% respectively).100 Furthermore, women who experienced trauma are more likely to be
obese101 and adverse experiences seem to be related to binge eating and the development of
obesity102, mainly when PTSD symptoms are present.103
Traumatic events and sexual function
Of all types of trauma, sexual trauma types have been studied most in relation to female sexual dysfunction and often show a profound effect.87,88 Traumatic experiences other than sexual
trauma, such as non-interpersonal trauma, have hardly been addressed in relation to sexual function.87,88 A recent review proposed that the relationship between sexual trauma and sexual
dysfunction is mainly driven by PTSD symptoms.83 It is thought that physical sensations of sexual
arousal during sexual activity can be misinterpreted as threat rather than pleasure during heightened arousal states in PTSD.82,83 The type of traumatic event in this regard may therefore
be less important, suggesting that also after other than sexual trauma types, a relationship between trauma exposure and sexual dysfunction may occur.
Pelvic floor overactivity and sexual function
The function of pelvic floor muscles is critical to sexual function, as a normal tonic pelvic floor seems to be associated with better sexual function.104 The pelvic floor is involved in stress
response and emotional processing, and is neuronally linked though the central nervous system to the limbic system.105,106 Trauma- and stress-related disorders can lead to an overactive pelvic
floor, as part of a trauma-related defence mechanism.107 Pelvic floor overactivity can lead to
physical symptoms, such as micturition complaints, defecation problems, and sexual problems including pain during sexual intercourse.107–109 Furthermore, almost half of the women with
chronic pelvic pain as part of an overactive pelvic floor reports a history of either sexual or physical abuse, and a quarter of them screens positive for PTSD.110 The association with pelvic
floor overactivity may therefore be due to the development of PTSD resulting from trauma.110
In chapter 7 of this dissertation we therefore aimed examine the effects of lifetime traumatic experiences and subsequent PTSD symptoms on sexual function and pelvic floor activity.
Polycystic ovary syndrome
Polycystic ovary syndrome (PCOS) is a common chronic heterogeneous disorder in women of reproductive age worldwide.111 The three main characteristics of PCOS are: anovulation,
hyperandrogenism and the presence of polycystic ovaries.112 Features of appearance in
1
though loss of their feminine identity and may account for emotional distress.113–115 Furthermore,
clinical features such as: infertility, obesity, insulin resistance, type II diabetes, dyslipidaemia, hypertension and metabolic syndrome116 are a risk factor for cardiometabolic disease in
women with PCOS.117 PCOS and its associated symptom profile can have an negative effect
on sexual function118 and mental health.119 Higher rates of depression and anxiety120,121, and a
lower quality of life122 have been found in women with PCOS compared to a healthy controls.121
However, studies investigating the effects of PCOS on mental health and sexual function mostly do not match the PCOS and control groups in characteristics, such as infertility status and the degree of obesity, this may lead to confounding. In chapter 6 of this dissertation we therefore aimed to investigate if mental health and sexual function differed in women with and without PCOS with a comparable BMI and fertility characteristics.
The LIFEstyle study
This dissertation is based upon the data of two studies: the LIFEstyle study and the WOMB project; a follow-up of women and children of the LIFEstyle study. The LIFEstyle study is a multicentre randomised controlled trial including 577 women of reproductive age (18 to 39 years) with infertility, a BMI ≥29 kg/m2 and a wish to conceive. Women were asked to
participate in one of the 23 medical centres in the Netherlands between 2009 and 2012. Women were then randomised into the intervention- or control group of the study. The women in the intervention group received a six-month structured preconception lifestyle intervention program. The main outcome of the study was a healthy at-term born singleton.
The lifestyle program consisted of a combination of dietary counselling, recommendations to increase physical activity, and behavioural counselling. Within the intervention period, six individual face-to-face consultations and four telephone or e-mail consultations were planned with a trained intervention coach. Women were advised to eat a healthy diet28 with a caloric
restriction of 600 kcal per day compared to their habitual intake, but not below 1200 kcal per day. Furthermore, women were advised to be moderately physically active for at least 2-3 times per week with a minimum of 30 minutes per day. And they were advised to increase their physical activity by taking at least 10.000 steps per day, which was monitored by a pedometer.
The main goal of the intervention was a preconception weight loss of at least 5% of their original bodyweight. When the target weight reduction was met or BMI decreased to below 29 kg/m2, women could proceed with fertility treatment. When a women became pregnant the
intervention was discontinued and women could re-enter in case of a miscarriage. The women in the control group received immediate fertility treatment, irrespective of their BMI.
The WOMB project
Between 2015 and 2017, on average five and a half years after randomisation in the LIFEstyle study, women were asked to participate in the WOMB project. WOMB is an acronym for
Women, their Offspring and iMproving lifestyle for Better cardiovascular health of both.
During this follow-up, data was gathered on a broad spectrum of outcomes directly- or indirectly related to cardiometabolic health, obesity, and infertility, both from the women that participated in the LIFEstyle study and the children that were conceived within the LIFEstyle study and born up to 24 months after randomization.
Part I of this dissertation focuses on both the short term effects of the preconception intervention during the LIFEstyle study on women’s lifestyle and the long term effects of the preconception intervention on women’s lifestyle during the WOMB project. Part II focuses entirely on the outcomes studied within the WOMB project.
Within this thesis, the following hypothesis was examined (Figure 1.3): Women with obesity and the wish to conceive, who participated in a preconception lifestyle intervention program to reduce weight, improve their short- and long-term lifestyle, mental health, quality of life and sexual function. Obese & wish to conceive
Improving
lifestyle before
pregnancy
• Lower cardiometabolic risks • Higher chances of getting
pregnant Long-term improved lifestyle Better mental health Better sexual function Better quality of life
1
O U T L I N E O F T H I S D I S S E R T A T I O N
Part I of this dissertation evaluates the effects of a preconception lifestyle intervention in women with obesity on short and long term diet and physical activity. Furthermore, we evaluated determinants of successful short term lifestyle change.
Chapter 2 of this dissertation reports the effects of a preconception lifestyle intervention on short-term diet and physical activity in the LIFEstyle RCT.
In chapter 3 the demographic, (bio)physical, behavioural and psychological determinants of short-term successful lifestyle change and program completion are investigated in the intervention arm of the LIFEstyle RCT.
In chapter 4 the effect of a lifestyle intervention on long term energy intake, diet quality and physical activity are examined in the WOMB project follow-up.
Part II of this dissertation evaluates whether a lifestyle intervention improves sexual function on the long term. Furthermore, the mental health and sexual function in women with obesity and PCOS is compared to controls with a comparable BMI and evaluates the relationship between traumatic life events, subsequent PTSD symptoms and sexual function and pelvic floor overactivity.
Chapter 5 reports the effects of a lifestyle intervention on sexual function 5 years after inclusion in the LIFEstyle RCT.
In chapter 6 we investigated whether women with PCOS and obesity differ with respect to controls in the domains: anxiety and depression, quality of life and sexual function.
In chapter 7 we examined the effects of traumatic life events and subsequent PTSD symptoms on pelvic floor overactivity and sexual functioning.
In chapter 8 the results and implications of this dissertation are discussed and put into a broader perspective.
R E F E R E N C E S
1. World Health Organization. Obesity and overweight. (2018). Available at: https:// www.who.int/news-room/fact-sheets/ detail/obesity-and-overweight. (Accessed: 3rd October 2019)
2. Chooi, Y. C., Ding, C. & Magkos, F. The epidemiology of obesity. Metabolism 92, 6–10 (2019).
3. Caballero, B. The Global Epidemic of Obesity: An Overview. Epidemiol. Rev. 29, 1–5 (2007).
4. NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet (London, England) 387, 1377–1396 (2016).
5. OECD & European Observatory on Health Systems and. Netherlands: Country Health
Profile 2017. (OECD Publishing, 2017).
6. Gezondheidsmonitor Volwassenen. Overgewicht, Cijfers & Context, Huidige situatie. 19-03-2019 (2018). Available at: https://www.volksgezondheidenzorg.info/ onderwerp/overgewicht/cijfers-context/ huidige-situatie#node-overgewicht-volwassenen-naar-leeftijd-en-geslacht. (Accessed: 18th November 2019) 7. National Institutes of Health (U.S.). NIH
Curriculum Supplement Series: Information about Energy Balance. (The Institutes,
2007).
8. Hruby, A. & Hu, F. B. The Epidemiology of Obesity: A Big Picture. Pharmacoeconomics 33, 673–89 (2015).
9. Lake, A. & Townshend, T. Obesogenic environments: exploring the built and food
environments. J. R. Soc. Promot. Health 126, 262–7 (2006).
10. Maury, E. & Brichard, S. M. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Molecular and
Cellular Endocrinology 314, 1–16 (2010). 11. Khan, S. S. et al. Association of Body Mass
Index With Lifetime Risk of Cardiovascular Disease and Compression of Morbidity.
JAMA Cardiol. 3, 280 (2018).
12. Lauby-Secretan, B. et al. Body Fatness and Cancer — Viewpoint of the IARC Working Group. N. Engl. J. Med. 375, 794–798 (2016).
13. Luppino, F. S. et al. Overweight, obesity, and depression: A systematic review and meta-analysis of longitudinal studies.
Archives of General Psychiatry 67, 220–229 (2010).
14. van der Steeg, J. W. et al. Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women. Hum. Reprod. 23, 324–8 (2008).
15. Gesink Law, D. C., Maclehose, R. F. & Longnecker, M. P. Obesity and time to pregnancy. Hum. Reprod. 22, 414–420 (2006).
16. Giviziez, C. R. et al. Obesity and
anovulatory infertility: A review. JBRA Assist.
Reprod. 20, 240–245 (2016).
17. Ramachenderan, J., Bradford, J. & McLean, M. Maternal obesity and pregnancy complications: A review. Aust. New Zeal. J.
Obstet. Gynaecol. 48, 228–235 (2008). 18. Catalano, P. M. & Shankar, K. Obesity and
pregnancy: Mechanisms of short term and long term adverse consequences for mother and child. BMJ 356, j1 (2017).
1
19. Yu, Z. et al. Pre-Pregnancy Body Mass Index in Relation to Infant Birth Weight and Offspring Overweight/Obesity: A Systematic Review and Meta-Analysis. PLoS
One 8, e61627 (2013).
20. Perng, W., Gillman, M. W., Mantzoros, C. S. & Oken, E. A prospective study of maternal prenatal weight and offspring cardiometabolic health in midchildhood.
Ann. Epidemiol. 24, 793-800.e1 (2014). 21. Kaar, J. L. et al. Maternal Obesity,
Gestational Weight Gain, and Offspring Adiposity: The Exploring Perinatal Outcomes among Children Study. J. Pediatr. 165, 509–515 (2014).
22. Gademan, M. G. J. et al. Maternal Prepregnancy Body Mass Index and Their Children’s Blood Pressure and Resting Cardiac Autonomic Balance at Age 5 to 6 Years. Hypertension 62, 641–647 (2013). 23. Oostvogels, A. J. J. M. et al. Maternal
Prepregnancy BMI, Offspring’s Early Postnatal Growth, and Metabolic Profile at Age 5–6 Years: the ABCD Study. J.
Clin. Endocrinol. Metab. 99, 3845–3854 (2014).
24. Reynolds, R. M. et al. Maternal obesity during pregnancy and premature mortality from cardiovascular event in adult offspring: Follow-up of 1 323 275 person years. BMJ 347, (2013).
25. National Institutes of Health (NIH). Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: executive summary. Expert Panel on the Identification, Evaluation, and Treatment of Overweight in Adults. Am. J. Clin. Nutr. 68, 899–917 (1998).
26. Klein, S. et al. Clinical implications of obesity with specific focus on cardiovascular disease: a statement for professionals from
the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 110, 2952–67 (2004).
27. Stegenga, H., Haines, A., Jones, K., Wilding, J. & Guideline Development Group. Identification, assessment, and management of overweight and obesity: summary of updated NICE guidance. BMJ 349, g6608 (2014).
28. Health Council of the Netherlands (Gezondheidsraad). Richtlijnen goede
voeding. (2015).
29. World Health Organization. Physical Activity. Global Strategy on Diet, Physical
Activity and Health (2017). Available at:
https://www.who.int/dietphysicalactivity/ pa/en/. (Accessed: 5th October 2019) 30. Middleton, K. R., Anton, S. D. & Perri, M. G.
Long-Term Adherence to Health Behavior Change. Am. J. Lifestyle Med. 7, 395–404 (2013).
31. Kelly, M. P. & Barker, M. Why is changing health-related behaviour so difficult? Public
Health 136, 109–116 (2016).
32. Berkman, E. T. The neuroscience of goals and behavior change. Consult. Psychol. J. 70, 28–44 (2018).
33. Bouton, M. E. Why behavior change is difficult to sustain. Prev. Med. (Baltim). 68, 29–36 (2014).
34. Birch, L., Savage, J. S. & Ventura, A. Influences on the Development of Children’s Eating Behaviours: From Infancy to Adolescence. Can. J. Diet. Pract. Res. 68, s1–s56 (2007).
35. Gardner, B. A review and analysis of the use of ‘habit’ in understanding, predicting and influencing health-related behaviour.
36. Rössner, S., Hammarstrand, M., Hemmingsson, E., Neovius, M. & Johansson, K. Long-term weight loss and weight-loss maintenance strategies. Obes.
Rev. 9, 624–630 (2008).
37. Van Sluijs, E. M. F., Van Poppel, M. N. M. & Van Mechelen, W. Stage-based lifestyle interventions in primary care: Are they effective? American Journal of Preventive
Medicine 26, 330–343 (2004). 38. Wing, R. R. & Hill, J. O. Successful weight
loss maintenance. Annu. Rev. Nutr. 21, 323–341 (2001).
39. Franz, M. J. et al. Weight-Loss Outcomes: A Systematic Review and Meta-Analysis of Weight-Loss Clinical Trials with a Minimum 1-Year Follow-Up. J. Am. Diet. Assoc. 107, 1755–1767 (2007).
40. Avenell, A. et al. Systematic review of the long-term effects and economic consequences of treatments for obesity and implications for health improvement. Health
Technol. Assess. 8, iii–iv, 1–182 (2004). 41. Chapman, K. Can people make healthy changes to their diet and maintain them in the long term? A review of the evidence.
Appetite 54, 433–441 (2010).
42. Wing, R. R. & Phelan, S. Long-term weight loss maintenance. Am. J. Clin. Nutr. 82, 222S-225S (2005).
43. Teixeira, P. J., Going, S. B., Sardinha, L. B. & Lohman, T. G. A review of psychosocial pre-treatment predictors of weight control. Obes.
Rev. 6, 43–65 (2005).
44. Mutsaerts, M. A. Q., Kuchenbecker, W. K. H., Mol, B. W., Land, J. A. & Hoek, A. Dropout is a problem in lifestyle intervention programs for overweight and obese infertile women: a systematic review. Hum. Reprod. 28, 979–86 (2013).
45. Moroshko, I., Brennan, L. & O’Brien, P. Predictors of dropout in weight loss interventions: a systematic review of the literature. Obes. Rev. 12, 912–934 (2011). 46. Marteau, T. M., Hollands, G. J. & Kelly,
M. P. Changing Population Behavior and Reducing Health Disparities: Exploring the Potential of “Choice Architecture” Interventions. in Population Health:
Behavioral and Social Science Insights (eds.
Kaplan, R. M. & Spittel, Michael L. David, D. H.) 105–127 (Department of Health and Human Services (HHS),Agency for Healthcare Research and Quality (AHRQ)). 47. Speck, B. J. & Harrell, J. S. Maintaining
regular physical activity in women: Evidence to date. J. Cardiovasc. Nurs. 18, 282–293 (2003).
48. Teixeira, P. J. et al. Successful behavior change in obesity interventions in adults: a systematic review of self-regulation mediators. BMC Med. 13, 84 (2015) 49. Altfeld, S., Handler, A., Burton, D. &
Berman, L. Wantedness of pregnancy and prenatal health behaviors. Women Health 26, 29–43 (1997).
50. Phelan, S. Pregnancy: a ‘teachable moment’ for weight control and obesity prevention.
Am. J. Obstet. Gynecol. 202, 135.e1-135. e8 (2010).
51. Hotham, E., Ali, R., White, J. & Robinson, J. Pregnancy-related changes in tobacco, alcohol and cannabis use reported by antenatal patients at two public hospitals in South Australia. Aust. New Zeal. J. Obstet.
Gynaecol. 48, 248–254 (2008).
52. McBride, C. M., Emmons, K. M. & Lipkus, I. M. Understanding the potential of teachable moments: The case of smoking cessation.
1
53. Masters, W. H. & Johnson, V. E. Human
sexual response. (Little Brown, 1966).
54. Basson, R. Human Sex-Response Cycles. J.
Sex Marital Ther. 27, 33–43 (2001). 55. American Psychiatric Association.
Diagnostic and Statistical Manual of Mental Disorders (5th ed.). (American Psychiatric
Association, 2013). doi:10.1176/appi. books.9780890425596
56. Kolotkin, R. L., Zunker, C. & Østbye, T. Sexual Functioning and Obesity: A Review.
Obesity 20, 2325–2333 (2012).
57. Rowland, D. L., McNabney, S. M. & Mann, A. R. Sexual Function, Obesity, and Weight Loss in Men and Women. Sex. Med. Rev. 5, 323–338 (2017).
58. Rosen, R. C. & Barsky, J. L. Normal Sexual Response in Women. Obstetrics and
Gynecology Clinics of North America 33, 515–526 (2006).
59. Althof, S. E. et al. Psychological and interpersonal dimensions of sexual function and dysfunction. J. Sex. Med. 2, 793–800 (2005).
60. Kolotkin, R. L. et al. Obesity and Sexual Quality of Life. Obesity 14, 472–479 (2006).
61. Yaylali, G. F., Tekekoglu, S. & Akin, F. Sexual dysfunction in obese and overweight women. Int. J. Impot. Res. 22, 220–226 (2010).
62. Esposito, K. et al. Association of body weight with sexual function in women. Int. J.
Impot. Res. 19, 353–357 (2007). 63. Pichlerova, D. et al. Sexual Dysfunctions in
Obese Women Before and After Bariatric Surgery. Med. Sci. Monit. 25, 3108–3114 (2019).
64. Assimakopoulos, K. et al. Bariatric Surgery is Associated with Reduced Depressive Symptoms and Better Sexual Function in
Obese Female Patients: A One-Year Follow-Up Study. Obes. Surg. 21, 362–366 (2011).
65. Rowland, D. L., McNabney, S. M. & Mann, A. R. Sexual Function, Obesity, and Weight Loss in Men and Women. Sex. Med. Rev. 5, 323–338 (2017).
66. Di Francesco, S., Caruso, M., Robuffo, I., Militello, A. & Toniato, E. The Impact of Metabolic Syndrome and Its Components on Female Sexual Dysfunction: A Narrative Mini-Review. Curr. Urol. 12, 57–63 (2019). 67. Schulster, M. L., Liang, S. E. & Najari,
B. B. Metabolic syndrome and sexual dysfunction. Curr. Opin. Urol. 27, 435–440 (2017).
68. Sarwer, D. B. et al. Changes in sexual functioning and sex hormone levels in women following bariatric surgery. JAMA
Surg. 149, 26–33 (2014).
69. Berman, J. & Bassuk, J. Physiology and pathophysiology of female sexual function and dysfunction. World J. Urol. 20, 111–118 (2002).
70. Rosato, E. et al. Clitoral blood flow in systemic sclerosis women: correlation with disease clinical variables and female sexual dysfunction. Rheumatology 52, 2238–2242 (2013).
71. Nappi, R. et al. Clinical biologic pathophysiologies of women’s sexual dysfunction. J. Sex. Med. 2, 4–25 (2005). 72. Quinn-Nilas, C., Benson, L., Milhausen, R. R., Buchholz, A. C. & Goncalves, M. The Relationship Between Body Image and Domains of Sexual Functioning Among Heterosexual, Emerging Adult Women. Sex.
Med. 4, e182-9 (2016).
73. Weinberger, N. A., Kersting, A., Riedel-Heller, S. G. & Luck-Sikorski, C. Body Dissatisfaction in Individuals with Obesity
Compared to Normal-Weight Individuals: A Systematic Review and Meta-Analysis.
Obes. Facts 9, 424–441 (2017). 74. Aversa, A. et al. Weight Loss by
Multidisciplinary Intervention Improves Endothelial and Sexual Function in Obese Fertile Women. J. Sex. Med. 10, 1024– 1033 (2013).
75. Wing, R. R. et al. Effect of intensive lifestyle intervention on sexual dysfunction inwomen with type 2 diabetes: Results from an ancillary look ahead study. Diabetes Care 36, 2937–2944 (2013).
76. Basson, R. & Gilks, T. Women’s sexual dysfunction associated with psychiatric disorders and their treatment. Womens.
Health (Lond. Engl). 14, (2018).
77. Wang, V. et al. Sexual health and function in later life: a population-based study of 606 older adults with a partner. Am. J. Geriatr.
Psychiatry 23, 227–33 (2015).
78. Kalmbach, D. A., Ciesla, J. A., Janata, J. W. & Kingsberg, S. A. Specificity of Anhedonic Depression and Anxious Arousal with Sexual Problems Among Sexually Healthy Young Adults. J. Sex. Med. 9, 505–513 (2012).
79. Cyranowski, J. M. et al. Lifetime Depression History and Sexual Function in Women at Midlife. Arch. Sex. Behav. 33, 539–548 (2004).
80. Mitchell, K. R. et al. Sexual function in Britain: findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). Lancet 382, 1817–1829 (2013). 81. Leeners, B., Hengartner, M. P., Rössler,
W., Ajdacic‐Gross, V. & Angst, J. The Role of Psychopathological and Personality Covariates in Orgasmic Difficulties: A Prospective Longitudinal Evaluation in a
Cohort of Women from Age 30 to 50. J.
Sex. Med. 11, 2928–2937 (2014). 82. Bradford, A. & Meston, C. M. The impact of
anxiety on sexual arousal in women. Behav.
Res. Ther. 44, 1067–77 (2006).
83. Yehuda, R., Lehrner, A. m. y. & Rosenbaum, T. Y. PTSD and Sexual Dysfunction in Men and Women. J. Sex. Med. 12, 1107–1119 (2015).
84. La Torre, A., Giupponi, G., Duffy, D. & Conca, A. Sexual Dysfunction Related to Psychotropic Drugs: A Critical Review - Part I: Antidepressants. Pharmacopsychiatry 46, 191–199 (2013).
85. Bijlsma, E. Y. et al. Sexual side effects of serotonergic antidepressants: Mediated by inhibition of serotonin on central dopamine release? Pharmacol. Biochem. Behav. 121, 88–101 (2014).
86. Cartwright, C., Gibson, K., Read, J., Cowan, O. & Dehar, T. Long-term antidepressant use: patient perspectives of benefits and adverse effects. Patient
Prefer. Adherence Volume 10, 1401–1407 (2016).
87. Pulverman, C. S., Kilimnik, C. D. & Meston, C. M. The Impact of Childhood Sexual Abuse on Women’s Sexual Health: A Comprehensive Review. Sex Med Rev 6, 188–200 (2018).
88. Pulverman, C. S. & Creech, S. K. The Impact of Sexual Trauma on the Sexual Health of Women Veterans: A Comprehensive Review. Trauma, Violence,
Abus. 152483801987091 (2019).
doi:10.1177/1524838019870912 89. O’Driscoll, C. & Flanagan, E. Sexual
problems and post-traumatic stress disorder following sexual trauma: A meta-analytic review. Psychology and Psychotherapy:
1
Theory, Research and Practice 89,351–367 (2016).
90. Shahhosseini, Z., Gardeshi, Z. H., Pourasghar, M. & Salehi, F. A review of affecting factors on sexual satisfaction in women. Mater. Sociomed. 26, 378–81 (2014).
91. Sánchez-Fuentes, M. del M., Santos-Iglesias, P. & Sierra, J. C. A systematic review of sexual satisfaction. Int. J. Clin.
Heal. Psychol. 14, 67–75 (2014). 92. Velten, J. & Margraf, J. Satisfaction
guaranteed? How individual, partner, and relationship factors impact sexual satisfaction within partnerships. PLoS One 12, e0172855 (2017).
93. Dewitte, M. & Mayer, A. Exploring the Link Between Daily Relationship Quality, Sexual Desire, and Sexual Activity in Couples.
Arch. Sex. Behav. 47, 1675–1686 (2018). 94. Wasow, M. Sexuality and the
institutionalized mentally ill. Sex. Disabil. 3, 3–16 (1980).
95. Peitl, M. V., Peitl, V. & Pavlović, E. Sexual self-perception in schizophrenic and depressive patients. Nord. J. Psychiatry 65, 306–310 (2011).
96. McCann, E. Investigating mental health service user views regarding sexual and relationship issues. J. Psychiatr. Ment. Health
Nurs. 17, 251–259 (2010). 97. Benjet, C. et al. The epidemiology of
traumatic event exposure worldwide: results from the World Mental Health Survey Consortium. Psychol. Med. 46, 327–343 (2016).
98. Snijders, C. et al. Resilience Against Traumatic Stress: Current Developments and Future Directions. Front. psychiatry 9, 676 (2018).
99. Liu, R. T. A developmentally informed perspective on the relation between stress and psychopathology: When the problem with stress is that there is not enough. J.
Abnorm. Psychol. 124, 80–92 (2015). 100. Kessler, R. C. et al. Trauma and PTSD in the
WHO World Mental Health Surveys. Eur. J.
Psychotraumatol. 8, 1353383 (2017). 101. van den Berk-Clark, C. et al. Association
between posttraumatic stress disorder and lack of exercise, poor diet, obesity, and co-occuring smoking: A systematic review and meta-analysis. Heal. Psychol. (2018). doi:10.1037/hea0000593
102. Palmisano, G. L., Innamorati, M. & Vanderlinden, J. Life adverse experiences in relation with obesity and binge eating disorder: A systematic review. J. Behav.
Addict. 5, 11–31 (2016).
103. de Vries, G.-J., Mocking, R. & Olff, M. Severity of posttraumatic stress disorder and the exposure-response relationship with body weight. (2019).
104. Rosenbaum, T. Y. Pelvic Floor Involvement in Male and Female Sexual Dysfunction and the Role of Pelvic Floor Rehabilitation in Treatment: A Literature Review. J. Sex. Med. 4, 4–13 (2007).
105. Blok, B. F. & Holstege, G. The neuronal control of micturition and its relation to the emotional motor system. Prog. Brain Res. 107, 113–26 (1996).
106. Holstege, G. The emotional motor system and micturition control. Neurourology and
Urodynamics 29, 42–48 (2010). 107. Laan, E. & van Lunsen, R. The overactive
pelvic floor: Female sexual functioning. in
The overactive pelvic floor (eds. Padoa,
A. & Rosenbaum, T. Y.) 17–29 (Springer International Publishing, 2016).
108. Hooker, A. B. et al. Chronic pelvic pain: evaluation of the epidemiology, baseline demographics, and clinical variables via a prospective and multidisciplinary approach.
Clin. Exp. Obstet. Gynecol. 40, 492–8 (2013).
109. Paras, M. L. et al. Sexual abuse and lifetime diagnosis of somatic disorders: A systematic review and meta-analysis. JAMA - Journal
of the American Medical Association 302, 550–561 (2009).
110. Meltzer-Brody, S. et al. Trauma and posttraumatic stress disorder in women with chronic pelvic pain. Obstet. Gynecol. 109, 902–8 (2007).
111. Azziz, R. et al. Polycystic ovary syndrome.
Nat. Rev. Dis. Prim. 2, 16057 (2016). 112. Fauser, B. C. J. M. Revised 2003 consensus
on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.
Fertil. Steril. (2004). doi:10.1016/j.
fertnstert.2003.10.004
113. Janssen, O., Hahn, S., Tan, S., Benson, S. & Elsenbruch, S. Mood and Sexual Function in Polycystic Ovary Syndrome. Semin. Reprod.
Med. 26, 045–052 (2008). 114. Conaglen, H. M. & Conaglen, J. V.
Sexual desire in women presenting for antiandrogen therapy. J. Sex Marital Ther. 29, 255–267 (2003).
115. Chachamovich, J. R. et al. Investigating quality of life and health-related quality of life in infertility: A systematic review.
Journal of Psychosomatic Obstetrics and Gynecology 31, 101–110 (2010).
116. Fauser, B. C. J. M. et al. Consensus on womens health aspects of polycystic ovary syndrome (PCOS). Hum. Reprod. 27, 14–24 (2012).
117. Aziz, M. et al. Polycystic ovary syndrome: cardiovascular risk factors according to specific phenotypes. Acta Obstet. Gynecol.
Scand. 94, 1082–1089 (2015). 118. Pastoor, H. et al. Sexual function in
women with polycystic ovary syndrome: a systematic review and meta-analysis.
Reprod. Biomed. Online 37, 750–760 (2018).
119. International PCOS Network et al.
International evidence-based guideline for the assessment and management of polycystic ovary syndrome. (2018).
120. Cooney, L. G. & Dokras, A. Depression and Anxiety in Polycystic Ovary Syndrome: Etiology and Treatment. Current Psychiatry
Reports 19, (2017).
121. Veltman-Verhulst, S. M., Boivin, J., Eijkemans, M. J. C. & Fauser, B. J. C. M. Emotional distress is a common risk in women with polycystic ovary syndrome: A systematic review and meta-analysis of 28 studies. Hum. Reprod. Update 18, 638–651 (2012).
122. Jones, G. L., Hall, J. M., Balen, A. H. & Ledger, W. L. Health-related quality of life measurement in women with polycystic ovary syndrome: a systematic review. Hum.
WOMEN’S
LIFESTYLE
CHAPTER 2
Effects of a preconception lifestyle intervention in
obese infertile women on diet and physical activity;
a secondary analysis of a randomized controlled trial
Tessa M. van Elten Matty D.A. Karsten Anouk Geelen Anne M. van Oers Mireille N.M. van Poppel Henk Groen Reinoud J.B.J. Gemke Ben Willem J. Mol Meike A.Q. Mutsaerts Tessa J. Roseboom* Annemieke Hoek*
* Authors contributed equally to this work Adapted from: PLoS ONE 2018 Nov; 13(11):e0206888
A B S T R A C T
Background: Lifestyle changes are notoriously difficult. Since women who intend to become pregnant are more susceptible to lifestyle advice, interventions during this time window might be more effective than interventions during any other period in life. We here report the effects of the first large preconception lifestyle intervention RCT on diet and physical activity in obese infertile women.
Methods: In total, 577 women were randomised between a six-month lifestyle intervention program (intervention group; N=290) or prompt infertility treatment (control group; N=287). Self-reported dietary behaviours and physical activity were assessed at baseline, three, six and twelve months after randomisation. Mixed models were used to analyse differences between groups.
Results: Compared to the control group, the intervention group reduced their intake of sugary drinks at three months (-0.5 glasses/day [95% C.I.-0.9;-0.2]), of savoury snacks at three (-2.4 handful/week [-3.4;-1.4]) and at six months (-1.4 handful/week [-2.6;-0.2]), and of sweet snacks at three (-2.2 portion/week [-3.3;-1.0]) and twelve months after randomisation (-1.9 portion/week [-3.5;-0.4]). Also, the intervention group was more moderate to vigorous physically active at three months after randomisation compared to the control group (169.0 minutes/week [6.0; 332.1]).
Conclusion: Our study showed that obese infertile women who followed a six-month preconception lifestyle intervention program decreased their intake of high caloric snacks and beverages, and increased their physical activity. These changes in lifestyle may not only improve women’s health but their offspring’s health too.
2
I N T R O D U C T I O N
The increasing prevalence of obesity is a major public health problem in women of reproductive age.1 Besides the association of obesity with increased prevalence of non-communicable
diseases2, it also adversely affects women’s reproductive health3,4, as well as offspring’s
health.5
A healthy lifestyle is recommended as the first step to control obesity.6 However, we do know
that structurally improving lifestyle is notoriously difficult. Women who intend to become pregnant are known to be more susceptible to lifestyle advice, for example to quit smoking and stop drinking alcohol.7,8 Therefore, lifestyle interventions prior to conception might be more
effective in changing diet and physical activity than interventions during any other period in life.
Up until now, studies mainly focused on intervening during the period of pregnancy9–14, but
currently attention shifts to intervention strategies targeting obese women before pregnancy to improve reproductive, maternal and child health.15–17 However, no experimental studies
assessing the effect of preconception lifestyle interventions in humans have been done yet. The LIFEstyle study was the first randomized controlled trial (RCT) designed to examine the efficacy of a preconception lifestyle intervention in a large group of obese infertile women on reproductive, gestational and delivery outcomes.18 The lifestyle intervention resulted in
significantly more weight loss19 and improved cardiometabolic health20, but it is unclear how
the intervention changed lifestyle.
Therefore, we here report the effects of the LIFEstyle preconception intervention program on diet and physical activity in obese infertile women throughout the intervention program and thereafter.
M A T E R I A L S A N D M E T H O D S
The LIFEstyle study was a multicentre RCT in obese infertile women (Dutch trial register; NTR 1530; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1530). Participants were included in the study between June 9, 2009 and June 22, 2012 and followed for two years. Design and primary results of the LIFEstyle study have been described previously.18,19 In brief,
the original study population consisted of 577 infertile women between 18 and 39 years old, with a BMI of ≥29 kg/m2. Women were eligible for recruitment when presenting with infertility
in a general or academic hospital. Infertility was defined as failure to conceive within 12 months of unprotected intercourse in case of an ovulatory cycle, or in case of chronic anovulation according to WHO class I or II. Couples were excluded if suffering from azoospermia or using donor semen, women with endometriosis AFS class III or IV, chronic anovulation WHO class III (premature ovarian failure) or endocrinopathies (such as Cushing syndrome, adrenal hyperplasia and diabetes type I). Women with untreated pre-existent hypertension, preeclampsia, eclampsia or HELLP syndrome in a previous pregnancy were also not eligible. This study was conducted according to the guidelines laid down in the Declaration of Helsinki. All procedures were approved by the Medical Ethics Committee of the University Medical Center Groningen, the Netherlands (METc 2008/284) and the review board of each participating centre. Written informed consent was obtained from all participants.
Intervention
Participants were randomized by a web-based randomization program at a central location, stratified according to trial centre and ovulatory status. Blinding was not possible due to the nature of the intervention. Participants randomized into the intervention arm participated in a six-month structured lifestyle program, aiming at a weight loss of 5-10% of the original body weight. After completion of the intervention program, if the target weight reduction of 5-10% was met, or if BMI decreased below 29 kg/m2, infertility treatment was started in accordance
with the Dutch infertility guidelines.21 When becoming pregnant participants discontinued
the intervention, but they could re-enter the intervention in case of a miscarriage. The control group promptly started infertility treatment based on the Dutch infertility guidelines. They did not receive any lifestyle advice with the exception of the patient information leaflet containing general information on the adverse effects of overweight and obesity on women’s reproductive health, pregnancy, and pregnancy outcomes.
The lifestyle program combined counselling on diet and physical activity with an individualized behavioural modification plan.22–24 Intervention nurses, with a background in infertility care,
were trained to guide and support the participants during six face-to-face and four telephone consultations.18 Participants were advised to consume a healthy diet according to the Dutch
2
dietary guidelines of 200625 with a caloric reduction of approximately 600kcal compared
to their usual caloric intake, but not below 1200 kcal/day. To create awareness of total food intake, participants could receive feedback on food and caloric intake on a daily basis using a web-based food diary of the Netherlands Nutrition Centre.26 Participants brought a copy of
these results to the consultations to discuss their dietary intake. In addition, participants were advised to be physically active 2-3 times a week for at least 30 minutes at moderate intensity (60-85% of maximum heart rate frequency), and to increase physical activity in daily life by taking 10.000 steps per day monitored with a pedometer. A diary was kept on these physical activities to establish self-monitoring, which was also used during the consultations to discuss physical activity levels.
Diet
Participants in both the intervention and the control group were asked to complete a food frequency questionnaire (FFQ) four times. Once at the start of the intervention, and at three, six and twelve months after randomization. The self-administered FFQ asked about foods and food groups the intervention focused on. It consisted of two parts: the first part includes the standardized questionnaire on food consumption used for the Public Health Monitor in the Netherlands.27 This first part has been supplemented with a second part, consisting of additional
frequency and portion size questions about snack intake and the usage of sugar containing and alcoholic beverages. Frequency of consumption was asked per week or per month. Portion size for all foods and food groups had been asked per standard household measure (e.g. glass or handful). We focused on the intake of vegetables (raw as well as cooked; grams/day), fruits (grams/day), sugary drinks (fruit juice and soda; glasses/day), alcoholic beverages (glasses/day) and the intake of savoury snacks (crisps, pretzels, nuts and peanuts; handful/ week) and sweet snacks (biscuits, pieces of chocolate, candies or liquorices; portion/week). One portion of sweet snacks included 2 biscuits, or 2 pieces of chocolate, or 5 candies, or 5 pieces of liquorice. Portion sizes and food groups as presented were pre-specified in the questions of the FFQ.
Physical activity
Participants completed the Short QUestionnaire to ASsess Health-enhancing physical activity (SQUASH) four times. Once at the start of the intervention, and at three, six and twelve months after randomization. The SQUASH is a validated questionnaire to rank subjects according to their level of physical activity.28 Data were collected about commuting activities, leisure time
activities, household activities, and activities at work and school, using three main questions: days per week, average time per day/week (hours and/or minutes), and intensity (low, moderate, high). We focused on the outcomes moderate to vigorous leisure time physical
activity (minutes/week), moderate to vigorous commuting activities (walking or cycling from/ to work or school; minutes/week) and moderate to vigorous total physical activity (MVPA; minutes/week).
Statistical methods
Differences and 95% confidence intervals (95% C.I.) in dietary intake as well as in physical activity between both groups at three, six and twelve months after randomization were analysed by mixed model analysis, using a random intercept. This method was chosen to account for decreasing response to questionnaires over time. All associations were adjusted for baseline values, using time and an interaction term between time and randomization group in the model. In addition, results are expressed as marginal means per time point, incorporating the dependency of observations within subjects and corrections for baseline. We checked if our data was normally distributed after adjusting for baseline values. To identify potential confounders, we adjusted for pregnancy, education level and smoking, one at the time, because of small, statistically non-significant differences between intervention and control group at baseline. If the effect estimate in the majority of the models changed >10%, we included the variable in the final model. To account for differences in the number of pregnant women in the intervention and control group, we tested for effect modification by adding pregnancy to the model and an interaction term with randomization group. Alcoholic beverages and commuting activities both had a median of zero in combination with a very narrow distribution, therefore we only showed medians and inter quartile rangers (IQR) for these variables (Supplementary Tables S2.2 and S2.3).
We additionally used univariate regression models to explore if weight change between baseline and six months after randomization (clinically measured weight in kg at 6 months minus clinically measured weight in kg at baseline) was related to changes in diet and physical activity between baseline and six months after randomization (physical activity/diet at 6 months minus physical activity/diet at baseline). Only total MVPA and diet variables that were statistically significant in our mixed model analyses were included. We performed these explorative analyses irrespective of randomization group, using complete cases while pregnant women were excluded.
All questions of the FFQ contained open answer categories for the largest portion size (e.g. more than 5 glasses of soda), with the exception of vegetable intake. As we did not know the exact portion size consumed when this answer was given, we arbitrarily chose to recode the portion size for these categories into X+1 (e.g. 6 glasses of soda). We performed a sensitivity analysis with X+1+30% (e.g. 8 glasses of soda) and found that the associations were robust (Supplementary Table S2.1).
2
Statistical analyses were performed using the software Statistical Package for the Social Sciences (SPSS) version 22 for Windows (SPSS, Chicago, IL, USA). P-values <0.05 were considered statistically significant.
R E S U L T S
Table 2.1 shows the characteristics of the study participants who completed the FFQ and/ or SQUASH at baseline (N=510). Characteristics were similar for the intervention group and the control group. There were no differences compared to the LIFEstyle study participants as a whole (N=574). Response decreased over time for both questionnaires (Figure 2.1). Supplementary Tables S2.2 and S2.3 show the dietary intakes and physical activity at baseline, three, six and twelve months after randomisation. After correction for baseline values, residuals were normally distributed. For diet and physical activity we found no significant interaction effect between pregnancy and randomisation group. Therefore, our model does not include an interaction term between pregnancy and randomisation group. Results were adjusted for pregnancy, education level and smoking based on their impact on the effect estimates.
Table 2.1. Characteristics of participants who completed the FFQ and/or SQUASH at baseline. Intervention group (N=261) Control group (N=249) P-value Age (mean; SD) 29.8 (4.5) 29.8 (4.5) 0.88 Caucasian (%; N) 89.3 (233) 89.2 (222) 0.97 Education (%; N)
Primary school (4-12 years) 6.0 (15) 2.9 (7) 0.26 Secondary education 24.0 (60) 23.4 (56)
Intermediate Vocational Education 49.2 (123) 47.7 (114) Higher Vocational Education and University 20.8 (52) 25.9 (62)
Smoking (yes; %; N) 26.1 (67) 21.4 (53) 0.22
Weight (kg; mean; SD) 103.7 (13.7) 103.4 (12.3) 0.80 Body Mass Index (kg/m2; mean; SD) 36.0 (3.4) 36.1 (3.4) 0.85 Anovulation (yes; %; N) 45.0 (117) 48.4 (120) 0.44
PCOS (%; N) 76.1 (89/117) 74.2 (89/120) 0.70
Nulliparous (%; N) 70.1 (183) 67.1 (167) 0.73
Baseline characteristics are presented as means and standard deviations (SD) for continuous variables, and as percentages (%) and total number of participants (N) for categorical data. To compare groups, an independent Student’s t-test was used for continuous variables, and a Chi-square test for categorical data; kg/m2 = kilograms per square meter; PCOS = Polycystic ovary syndrome.
822 women were eligible 577 were randomly assigned to intervention 245 were excluded 290 allocated to intervention group 287 allocated to control group 225588 FFFFQQ of which 10 pregnant 225555 SSQQUUAASSHH of which 10 pregnant 224488 FFFFQQ of which 7 pregnant 224433 SSQQUUAASSHH of which 6 pregnant Baseline 117711 FFFFQQ of which 24 pregnant 116666 SSQQUUAASSHH of which 22 pregnant Three months after randomisation 220088 FFFFQQ of which 48 pregnant 220044 SSQQUUAASSHH of which 47 pregnant 111111 FFFFQQ of which 23 pregnant 110088 SSQQUUAASSHH of which 22 pregnant Six months after randomisation 114477 FFFFQQ of which 55 pregnant 114466 SSQQUUAASSHH of which 54 pregnant 8800 FFFFQQ of which 33 pregnant 7788 SSQQUUAASSHH of which 33 pregnant Twelve months after randomisation 110077 FFFFQQ of which 32 pregnant 110077 SSQQUUAASSHH of which 32 pregnant 1 withdrew informed consent 2 withdrew informed consent 63 dropped-out of the intervention
Figure 2.1. Flow diagram LIFEstyle study for diet and physical activity data.
FFQ = Food Frequency Questionnaire; SQUASH = Short QUestionnaire to ASsess Health-enhancing physical activity; mo. = months.
2
Diet
Table 2.2 shows the overall differences in lifestyle between the intervention and control group, which represents the effect of randomisation group on the diet and physical activity outcomes irrespective of the effect of time, and the differences in lifestyle per time point after randomisation. There were overall group effects for the intake of sugary drinks (-0.4 glasses/ day [95% C.I.-0.6; -0.1]; Table 2.2), savoury snacks (-1.8 handful/week [-2.6; -0.9]), and sweet snacks (-1.8 portion/week [-2.8; -0.9]). The intervention group had a lower intake of sugary drinks at three months after randomisation compared to the control group (-0.5 glasses/day [-0.9; -0.2]). They also had a lower intake of savoury snacks at three months (-2.4 handful/week [-3.4; -1.4]) and at six months after randomisation (-1.4 handful/week [-2.6; -0.2]), and a lower intake of sweet snacks at three months (-2.2 portion/week [-3.3; -1.0]) and twelve months after randomisation (-1.9 portion/week [-3.5; -0.4]) compared to the control group.
Figure 2.2 shows the estimated marginal means for dietary intake and physical activity in the intervention and control group over the different time points. We tested if the effects of the intervention on the dietary intake and physical activity outcomes differed over time by adding an interaction term between time and randomisation group into our model. Interaction effects between time and randomisation group showed no significant results, with exception of savoury snacks (p=0.01). This is due to the large decrease in savoury snack intake in the intervention group compared to the control group at three months after randomisation (Figure 2.2). Explorative univariate regression analyses showed that weight loss during the first six months is related to decreased savoury snack intake during the first six months after randomisation (mean predicted value=-2.60 handful/week; P=0.01; total N=127). No other statistically significant associations between change in body weight and change in lifestyle behaviours were seen.
Physical activity
There was an overall group effect for total MVPA (133.6 minutes/week [3.0; 264.3]), but not for leisure time MVPA (Table 2.2). For total MVPA the difference between the intervention group and the control group was statically significant at three months after randomisation (169.0 minutes/week [6.0; 332.1]). Thereafter, differences between the intervention group and the control group decreased, although the intervention group was more physically active compared to the control group at all points in time. A similar pattern was seen in leisure time MVPA, but there were no statistically significant differences between the intervention and control group . Interaction effects between time and randomisation group showed no significant results.
Table 2.2. Differences in diet and physical activity in the intervention group compared to the control group. Overall
(95% C.I.)a
Time point after randomisation
Difference
(95% C.I.) P-value Vegetable intake (gram/day)
Corrected for baseline 6.3 (-4.1; 16.6)
Three months 5.2 (-6.9; 17.4) 0.40 Six months 13.2 (-1.0; 27.4) 0.07 Twelve months -3.3 (-19.2; 12.6) 0.69 Corrected for baseline, education,
pregnancy and smoking
4.0 (-6.8; 14.8)
Three months 3.1 (-9.5; 15.7) 0.63 Six months 10.7 (-4.1; 25.6) 0.16 Twelve months -4.9 (-21.6; 11.7) 0.56 Fruit intake (gram/day)
Corrected for baseline -0.5 (-11.8; 10.8)
Three months 7.2 (-6.8; 21.2) 0.32 Six months -12.3 (-28.9; 4.2) 0.14 Twelve months -0.7 (-19.6; 18.2) 0.94 Corrected for baseline, education,
pregnancy and smoking
0.7 (-10.8; 12.3)
Three months 8.9 (-5.3; 23.1) 0.22 Six months -8.7 (-25.5; 8.2) 0.31 Twelve months -5.3 (-24.6; 14.0) 0.59 Sugary drinks (glasses/day)
Corrected for baseline -0.4 (-0.7; -0.1)c
Three months -0.5 (-0.9; -0.2) 0.001 Six months -0.5 (-0.8; -0.1) 0.03 Twelve months 0.02 (-0.4; 0.5) 0.93 Corrected for baseline, education,
pregnancy and smoking
-0.4 (-0.7; -0.1)c
Three months -0.6 (-0.9; -0.2) 0.001 Six months -0.4 (-0.8; 0.02) 0.07 Twelve months -0.04 (-0.5; 0.4) 0.86 Savoury snacks (handful/week)
Corrected for baseline -1.8 (-2.7; -1.0)d
Three months -2.4 (-3.4; -1.4) <0.001 Six months -1.5 (-2.7; -0.3) 0.01 Twelve months -0.8 (-2.1; 0.5) 0.25 Corrected for baseline, education,
pregnancy and smoking
-1.7 (-2.6; -0.9)d
Three months -2.5 (-3.5; -1.5) <0.001 Six months -1.4 (-2.6; -0.2) 0.03 Twelve months -0.4 (-1.8; 0.9) 0.52 Sweet snacks (portion/week)b
Corrected for baseline -1.9 (-2.8; -1.0)d
Three months -2.3 (-3.4; -1.1) <0.001 Six months -1.4 (-2.8; -0.1) 0.04 Twelve months -1.8 (-3.3; -0.2) 0.03
