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Obesity and its complications in women
Haley Smith, BPharm, MRPharmS
Amayeza Information Centre
Correspondence to: Haley Smith, e-mail: [email protected]
Keywords: obesity, complications, women
Abstract
Obesity is a chronic disease that is increasing in prevalence in adults, adolescents and children. It is now considered to be a global
epidemic. It is estimated that more than one in three women are obese. Obesity impacts negatively on the health of women and
increases their risk of developing conditions such as heart disease, diabetes, stroke and cancer. By reducing their weight, obese
women can lower their risk of these conditions, and in some cases, control the disease. This article reviews the complications that are
associated with obesity in women.
© Medpharm
S Afr Pharm J 2012;79(10):26-30
Introduction
instead of walking are examples of lifestyle factors that may
promote weight gain and obesity.4,5
Obesity has become one of the most important public health
problems in today’s society. As the prevalence of obesity increases,
so does the prevalence of co-morbidities that are associated with
the disease.1 The aetiology of obesity appears to be multifactorial,
but common factors in all obesity situations is calorie intake in
excess of the body’s requirements, and low activity levels.2-4 The
success of any weight-reduction programme relies extensively
on the motivation of the obese patient, curbing energy intake,
correcting the balance of nutrients and participating in exercise
programmes. These should constitute the mainstay of the
approach in the management of obesity.
Genetic factors may interact with environmental factors to cause
obesity.5,7 Studies suggest that heritable factors are responsible
for 30-50% of the variation in adiposity. Over 30 genes with
polymorphisms that relate to obesity have been identified by
genome-wide scans.7
Obesity is more prevalent in adults with physical, sensory, or
mental health disabilities. Those with impaired lower extremity
mobility are at highest risk. Other factors associated with the
development of obesity include endocrine disorders, smoking
cessation and certain medications.5,7
Causes of obesity
Screening for obesity
Many factors play a role in a person becoming overweight or
obese, including behavioural, environmental, cultural and genetic
causes.
Evaluation of obese or overweight patients requires a
comprehensive approach. Assessment of the individual’s overall
risk status includes determining the degree of adiposity by
measuring:
An excess intake of calories, together with a sedentary lifestyle,
causes weight gain and may lead to obesity.5,6 Of all the
sedentary behaviours, prolonged television watching appears
to be the most predictive for an increase in the risk of obesity.5
Epidemiological data suggest that a diet that is high in saturated
fats, red or processed meats, refined carbohydrates and sugar is
associated with weight gain and obesity.5 Low levels of physical
and recreational activities also relate to weight gain, in both men
and women.4,5
• Body mass index (BMI), i.e. weight in kilograms divided by
height in metres squared
• Abdominal obesity (by measuring the waist circumference)
• Overall medical risk, i.e. co-morbidities.
The BMI is a measure of body fat based on height and weight
and is the most practical way to evaluate the degree of obesity,
although it is not sensitive to body composition, e.g. the BMI of
a body builder may be similar to that of a person who is simply
obese. By definition, a BMI greater than 30 kg/m2 indicates clinical
obesity.4,8-10
In an affluent society, energy-sparing devices in the workplace
and at home reduce energy expenditure and may enhance the
tendency to gain weight.5 Larger portions of food, little time to
exercise or cook healthy meals, and using cars to get to places
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Effects of obesity
pills in women aged 15-45 years revealed that oral contraceptives
further increased the effect of obesity on the risk of thrombosis,
leading to a 10-fold increased risk in women with a BMI that is
greater than 25 kg/m2.12,13
Obesity impacts negatively on the health of women. It has wideranging effects on reproductive health and may lead to chronic
medical conditions in women.9
Older obese women may be at higher risk of developing venous
thrombosis. Combination contraceptives should be used with
caution in women who are obese and who are older than 35
years.12
Obesity and infertility
Obesity affects fertility throughout a woman’s life. Excess body
fat relates to menstrual abnormalities, infertility, miscarriage
and difficulties in performing assisted reproduction. Usually,
subfertility in obese women relates to ovulatory dysfunction.
The ovulatory dysfunction relates to polycystic ovary syndrome
(PCOS) in some obese women. The impact of obesity and PCOS
on reproductive function can be attributed to multiple endocrine
mechanisms. Abdominal obesity is associated with an increase
in circulating insulin levels. This results in increased functional
androgen levels. Chronic elevation of circulating oestrogen is
caused by aromatisation in peripheral adipose tissue. In part, the
resulting hyperandrogenism and menstrual cycle abnormalities
are clinically manifested by anovulatory cycles and subfertility.
Obesity and pregnancy
Women with chronic conditions, such as obesity, are at higher risk
of pregnancy-related complications. Obesity causes complications
because of the elevated risks of antepartum complications
and mechanical difficulties with delivery. Pre-pregnancy
obesity contributes to the development of pregnancy-induced
hypertension, pre-eclampsia and gestational diabetes. Foetal
anomalies, such as neural tube defects; spina bifida; nonneural
tube defects of the central nervous system; a cleft lip and palate;
and great vessel, ventral wall and other intestinal defects have all
been associated with obesity.10,11
It is also important to note that even in ovulatory women,
increasing obesity is associated with decreasing spontaneous
pregnancy rates and increased time to pregnancy. The mechanism
may relate to the adverse effects of elevated insulin levels on
ovarian function. Obesity may also have a negative impact on
the outcome of treatment of infertility. It appears to affect the
outcome of in vitro fertilisation. Most studies have reported an
association between increased BMI and subfertility. In addition,
multiple observational studies have found that a reduction in
weight using exercise and diet in obese, infertile women was
associated with an increase in the frequency of ovulation and in
the likelihood of pregnancy.9-11
BMI > 30 kg/m2 is associated with an increased risk of spontaneous
abortion. The increased risk of miscarriage in obese women may be
because such women often have PCOS which has been associated
with a higher frequency of early pregnancy loss. Obese women
also have a high rate of Caesarean delivery and are more likely
to have surgical, anaesthetic and postpartum complications. 11,14
A meta-analysis that included nine controlled studies examined
the association between maternal obesity and the risk of stillbirth.
The analysis found that overweight and obese pregnant women
experienced significantly more stillbirths than normal-weight
women. Maternal obesity has also been associated with neonatal
death, largely from pregnancy complications or disorders leading
to preterm birth.11
Obesity and contraception
Obesity and type 2 diabetes
Counselling obese women about their contraception options
can be challenging. Many metabolic processes are affected by
adiposity. These changes in metabolism can affect contraceptive
efficacy potentially. There is some evidence that oral contraceptive
pharmacokinetics are altered in obese women, resulting in
inadequate hypothalmic-pituitary-ovarian suppression. However,
further studies are needed. Drug metabolism, drug distribution
in adipose tissue and a dilutional effect from having a larger
circulating blood volume, could affect the half-life of hormonal
contraceptives in obese women, thereby decreasing contraceptive
efficacy. There is some evidence that combined oral contraceptive
pills, the contraceptive patch and contraceptive implants are less
effective in women with a greater body weight. The intrauterine
device may be one of the few reliable contraceptive options,
whose efficacy does not seem to be affected by BMI, for obese
women who want the most effective reversible method of
contraception.9,12
The risk of diabetes mellitus increases with the degree and
duration of being overweight or obese, and with a central or
visceral distribution of body fat. Increased visceral fat enhances
the degree of insulin resistance that is associated with obesity. In
turn, insulin resistance and increased visceral fat are the hallmarks
of metabolic syndrome, an assembly of risk factors for the
development of diabetes and cardiovascular disease.
Obesity not only increases the risk of developing type 2 diabetes.
It also complicates its management. The presence of obesity
exacerbates the metabolic abnormalities of type 2 diabetes,
including hyperglycaemia, hypeinsulinaemia and dyslipidaemia.
Obesity also increases insulin resistance and glucose intolerance.
Obesity may contribute to excessive morbidity in patients with
type 2 diabetes.1,9,10,15,16
Obesity and cardiovascular disease
Obesity is an independent risk factor for venous thrombosis. This
risk is increased in users of oestrogen-containing contraceptives.
Evaluation of the combined effect of obesity and oral contraceptive
S Afr Pharm J
Obesity is an independent risk factor for the development of
coronary artery disease in women, and is an important modifiable
risk factor for the prevention thereof. With any given level of BMI,
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the risk of the development of cardiovascular disease in both men
and women is increased by greater amounts of abdominal fat, as
reflected in the increased waist:hip ratio.9,15,16
Blood pressure is often increased in obese patients and is probably
the most common co-morbidity that is associated with obesity.1,15
The risk of hypertension is greatest in those with upper body and
abdominal obesity. The mechanism by which upper body obesity
raises blood pressure is poorly understood. One theory proposes
that insulin resistance plays a central role, leading to impaired
glucose tolerance and hyperinsulinaemia. Hyperinsulinaemia may
then raise the blood pressure by increasing sympathetic activity,
renal sodium reabsorption or vascular tone.15
Obesity is associated with several deleterious changes in lipid
metabolism. Unfavourable obesity-related effects include
high serum concentrations of low-density lipoprotein (LDL)
cholesterol, very low-density lipoprotein (VLDL) cholesterol and
triglycerides and a reduction in serum high-density lipoprotein
(HDL) cholesterol. The latter may be most significant, since a low
serum HDL cholesterol carries a greater risk of coronary heart
disease than hypertriglyceridaemia.10,15
Obesity has been associated with an increased risk of deep vein
thrombosis and pulmonary embolism.15 In the absence of medical
co-morbidities, the degree to which age alone increases the risk
of venous thromboembolism is unclear. However, age appears to
increase the risk of co-morbidities, such as cardiovascular disease,
which is associated with venous thrombosis. Thus, older obese
women may be at a higher risk of venous thrombosis and should
be properly counselled about this risk.12
Obesity and musculoskeletal pain
Obesity has been implicated in the development or progression
of low back pain and knee osteoarthritis in women. Direct
mechanical stress on the intervertebral discs and the indirect
effects of atherosclerosis on blood flow to the lumbar spine are
suspected to be mechanisms through which obesity affects the
discs, leading to subsequent back pain.
Data that support the link between obesity and knee osteoarthritis
have suggested that obesity leads to an excess load on the
joint, increased cartilage turnover, increased collagen type 2
degradation products and an increased risk of degenerative
meniscal lesions.9
Obesity and depression
Although many social, psychological and cultural factors may
contribute to depression in obese women, one explanation argues
that the stigma that exists towards obese individuals may lead
to low self-esteem and, ultimately, depression. Another theory
argues that the pressure of trying to fit into a norm and continued
dieting may lead to depression.1,9
Urinary stress incontinence
Obesity is a well-documented risk factor for stress incontinence,
urge incontinence and urgency. Obesity was found to be a strong
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risk factor for several urinary symptoms after pregnancy and
delivery for as long as 6-18 months postpartum.10
Obesity and cancer in women
There is mounting evidence that obesity is a risk factor for
the development of cancers of the oesophagus, breast
(postmenopausal), endometrium, colon, rectum, kidney, pancreas, thyroid and gallbladder.9,17,18
The following mechanisms have been suggested to explain the
association between obesity and the increased risk of developing
certain cancers:17,18
• Often, obese people have increased levels of insulin and
insulin-like growth factor-1 in their blood (a condition known
as hyperinsulinaemia or insulin resistance), which may promote
the development of certain tumours.
• Fat tissue produces excess amounts of oestrogen, high levels of
which have been associated with the risk of breast, endometrial
and other cancers.
• Obese people often have chronic low-level or subacute
inflammation, which has been associated with an increased
cancer risk.
• Fat cells may have direct and indirect effects on tumour growth
regulators.
• Fat cells produce hormones, called adipokines, that may
stimulate or inhibit cell growth. For example, leptin, which
is more plentiful in obese people, seems to promote cell
proliferation, whereas adiponectin, which is less abundant in
obese people, may have antiproliferative effects.
Management of obesity
The optimal management of obesity includes a combination
of diet, exercise and behavioural modifications for a duration
of approximately three to six months for the majority of
patients.2,16,19,20
The use of pharmacological agents as adjunctive therapy for
weight management is universally recommended when an
individual has a BMI ≥ 30 kg/m2 and fails to achieve significant
weight loss with diet and exercise alone. In the presence of
obesity-related co-morbidities such as hypertension, diabetes
or dyslipidaemia, the cut-off point for the pharmacological
treatment recommendation is lowered to a BMI of 25-27 kg/m2.
Once the decision is made to initiate drug therapy, it is important
to emphasise to patients that drug therapy does not cure obesity.20
Available pharmacological options for weight loss in South Africa
include the following:2,20
• Adrenergic agonists, such as phentermine, phendimetrazine,
diethylpropion and cathine, i.e. norpseudoephedrine
• The combined serotonergic and adrenergic agonists, i.e.
sibutramine
• The lipase inhibitor, orlistat.
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Conclusion
10. The effect of obesity on women’s health: research overview. Health Check
Systems [homepage on the Internet]. c2012. Available from: http://www.
healthchecksystems.com/twomen.htm
Obesity is becoming more prevalent in today’s society. The
disease can have wide-ranging effects on a variety of women’s
health issues. The pharmacist is well placed to counsel women on
the complications that are associated with obesity, as well as on
measures that may be implemented to assist in weight loss.
11. Nuthalapaty FS, Rouse DJ. The impact of obesity on fertility and pregnancy.
UpToDate [homepage on the Internet]. 2012. c2012. Available from:
http://www.uptodate.com/contents/the-impact-of-obesity-on-fertilityand-pregnancy
12. Edelman A, Kaneshiro B. Contraception counseling for obese women.
UpToDate [homepage on the Internet].2011. c2012. Available from: http://
www.uptodate.com/contents/contraception-counseling-for-obesewomen
References
1. Klish W J. Comorbidities and complications of obesity in children and
adolescents. UpTo Date [homepage on the Internet]. 2012. c2012.
Available from: http://www.uptodate.com/contents/comorbidities-andcomplications-of-obesity-in-children-and-adolescents
13. Abdollahi M, Cushman M, Rosendaal FR. Obesity: risk of venous thrombosis
and the interaction with coagulation factor levels and oral contraceptive
use. PubMed [homepage on the Internet]. c2012. Available from: http://
www.ncbi.nlm.nih.gov/pubmed/12624633
2. South African Medicines Formulary. Cape Town: The Division of Clinical
Pharmacology, Faculty of Health Sciences, University of Cape Town.
3. Centres for Disease Control and Prevention. Overweight and obesity
[homepage on the Internet]. c2012. Available from: http://www.cdc.gov/
obesity/adult/index.html
14. Porreco RP. Cesarean delivery of the obese women. UpToDate [homepage
on the Internet]. 2012. c2012. Available from: http://www.uptodate.com/
contents/cesarean-delivery-of-the-obese-woman
4. Overweight, obesity, and weight loss fact sheet. Womenshealth.gov
[homepage on the Internet]. 2009. Available from: http://womenshealth.
gov/publications/our-publications/fact-sheet/overweight-weight-loss.
cfm
15. Bray GA. Health hazards associated with obesity in adults. UpToDate
[homepage on the Internet]. 2011. c2012. Available from: http://www.
uptodate.com/contents/health-hazards-associated-with-obesity-inadults
5. Bray GA. Etiology and natural history of obesity. UpToDate [homepage
on the Internet]. 2012. c2012. Available from: http://www.uptodate.com/
contents/etiology-and-natural-history-of-obesity
16. Jackson E, Rubenfire M. Obesity, weight reduction, and cardiovascular
disease. UpToDate [homepage on the Internet]. 2011. c2012. Available
from:
http://www.uptodate.com/contents/obesity-weight-reductionand-cardiovascular-disease
6. Bray GA. Role of physical activity and exercise in obesity. UpToDate
[homepage on the Internet]. 2011. c2012. Available from: http://www.
uptodate.com/contents/role-of-physical-activity-and-exercise-in-obesity
17. Obesity and cancer risk. National Cancer Institute [homepage on the
Internet]. c2012. Available from: http://www.cancer.gov/cancertopics/
factsheet/Risk/obesity
7. Bray GA. Pathogenesis of obesity. UpToDate [homepage on the Internet].
2012. c2012. Available from: http://www.uptodate.com/contents/
pathogenesis-of-obesity
18. Bianchini F, Kaaks R, Vainio H. Overweight, obesity, and cancer risk.
PubMed [homepage on the Internet]. c2012. Available from: http://www.
ncbi.nlm.nih.gov/pubmed/12217794
8. Bray GA. Screening for and clinical evaluation of obesity in adults.
UpToDate [homepage on the Internet]. 2011. c2012. Available from: http://
www.uptodate.com/contents/screening-for-and-clinical-evaluation-ofobesity-in-adults
19. Bray GA. Dietary therapy for obesity. UpToDate [homepage on the
Internet]. 2011. c2012. Available from: http://www.uptodate.com/
contents/dietary-therapy-for-obesity
9. Kulie T, Slattengren A, Redmer J, et al. Authors. Obesity and women’s
health: an evidence-based review. J Am Board Fam Med. 2011;24(1):7585 [homepage on the Internet]. Available from: http://www.jabfm.org/
content/24/1/75.full
S Afr Pharm J
20. GlaxoSmithKline pharmacists’ professional development. Prevention and
management of overweight and obesity: a challenge for South Africans.
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