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Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome

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Int J Cur Res Rev | Vol 12 • Issue 10 • May 2020 5
Etiology of Abnormal Uterine Bleeding in
Adolescents – Emphasis Upon Polycystic
Ovarian Syndrome
Anamul Haq*, Sheema, Shazieya Akhtar

ABSTRACT
Introduction: Abnormal uterine bleeding is a frequent reason for physician visits by adolescents and this menstrual disorder has
been shown to adversely affect quality of life. In Indian context, adolescents constitute 21.4% of the total population and this age
group needs special attention as these are the formative years of an individual when major changes take place.
Objectives: To evaluate polycystic ovarian syndrome as common cause for abnormal uterine bleeding in adolescents.
Methods: We studied 200 patients aged 10 to 20 years admitted in our department with abnormal uterine bleeding having
severe anemia or hemodynamic instability. On admission detailed history and clinical examination was taken. Hormonal testing
for PCOS and other necessary investigations were done.
Results: Of the 200 patients, the mean age was 15.2+2.4 years. Mean hemoglobin was 6.0+1.5 g. 40% patients were over-
weight/obese. PCOS accounted for 30% of admissions. Hypothalamic pituitary ovarian axis immaturity 30% of admissions, en-
dometritis (12%), bleeding disorders (14%). PCOS was more likely in overweight/obese females. Girls with HPOaxis immaturity
had hemoglobin less than other etiologies.
Conclusion: PCOS is the common underlying etiology in adolescents hospitalized with abnormal uterine bleeding. Screening is
important for early diagnosis to allow ongoing management and prevention of comorbidity.
Key Words: AUB, PCOS, Adolescents, Anemia
Corresponding Author:
Anamul Haq, Government Lalla Ded Hospital, an associated hospital of Govt. Medical College, Srinagar.
Email: anamulhaq801@gmail.com
ISSN: 2231-2196 (Print) ISSN: 0975-5241 (Online)
Received: 13.03.2020 Revised: 18.04.2020 Accepted: 03.05.2020
Research Article
International Journal of Current Research and Review
DOI: http://dx.doi.org/10.31782/IJCRR.2020.12102
IJCRR
Section: Healthcare
Sci. Journal Impact
Factor: 6.1 (2018)
ICV: 90.90 (2018)
INTRODUCTION
Menstrual disorders and abnormal uterine bleeding (AUB)
are among the most frequent gynecologic complaints of
adolescents.1,2 Abnormal uterine bleeding (AUB) is a term
coined to incorporate bleeding that is excessive or occurs
outside of normal cyclic menstruation.3 its importance lies in
the fact that AUB has a major impact on women’s quality of
life, pro ductivity and utilization of healthcare services.4 AUB
is defined as uterine bleeding lasting longer than 7 days, oc-
curring more frequently than every 21 days and ? or requir-
ing tampon or pad changes every 1-2 hours5.
World health organization has defined adolescence as a pe-
riod between 10-19 years. Abnormal uterine bleeding is a
frequent reason for physician visits by adolescent girls and
this menstrual disorder has been shown to adversely affect
adolescents quality of life6,7.
In India adolescents constitute over 21.4% of total popula-
tion and this age group needs special attention when major
physical, psychological and behavioral changes take place
and additional roles and responsibilities are expected from
them8,9. In India very little attention is paid to reproductive
health of adolescent girls comprising 22% females Reason
for neglect are ignorance, indifference, reluctance of parents
and girls to consult a doctor.
Mostly managed in OPDs but may develop severe sympto-
matic anemia and /or haemodynamic instability and require
urgent hospitalization. ACOG divided causes of AUB into
two groups PALM COEIN Structural and with non-structur-
al.
Structural abnormities include polyps, adenomyosis, leio-
myoma and malignancy.
Int J Cur Res Rev | Vol 12 • Issue 10 • May 2020 6
Haq et.al: Etiology of abnormal uterine bleeding in adolescents – emphasis upon polycystic ovarian syndrome
Non-structural abnormalities include bleeding disorders,
ovulatory dysfunction, endometrial, iatrogenic and not
classified causes of bleeding, most AUB episodes in ado-
lescents are non structural10. PCOS appears to underlie ir-
regular menses in up to one third of girls (Venturoli et al).
Menarche is not delayed but bleeding is then persistently
irregular.
Over the past years, several small review studies of adoles-
cents hospitalized for AUB with either severe anaemia or
haemodynamically unstable indicate that ovulatory dysfunc-
tion due to HPO immaturity as well as congenital or acquired
bleeding disorders are the two most common causes of AUB
requiring hospitalization.
In our study we hypothesized that ovulatory dysfunction re-
lated to PCOS would be a common underlying etiology as
we frequently diagnose PCOS in adolescents in the outpa-
tient settings.
AIMS AND OBJECTIVES
Etiology of AUB in adolescents.
To differentiate ovulatory dysfunction secondary to
PCOS from other causes.
Ovulatory dysfunction due to PCOS: a common un-
derlying etiology.
MATERIALS AND METHODS
All females aged 10 to 20 years admitted between Janu-
ary 2017 to January 2018 for treatment of acute menor-
rhagia with severe anemia or orthostatic hypotension. After
thorough history and examination, investigations including
blood tests to assess for bleeding disorders and hormonal
evaluations including PCOS were sent to laboratory prior
to beginning any treatment with hormonal medication or
blood transfusion. In this study, adolescent girls with dys-
function of PCOS were studied. Gynaecological age group
was defined as chronologic age at the time of the hospi-
talization minus age at menarche. HPO axis immaturity as
cause of AUB in adolescents if presenting just after puberty
within two years and rest of the causes are absent. We clas-
sified PCOS if their gynaecological age was greater than 2
years and they met Rotterdam criteria. USG criteria was not
used for PCOS as they are difficult to apply to adolescents.
Endometritis as the cause of AUB in subjects with positive
nucleic acid amplification test for chlamydia trachomatis
or neisseria gonorrhea without identification of any other
cause of AUB.
Table 1: Various Characteristics of adolescents admit-
ted to Lalla Ded Hospital (n=200)
Mean
Age (years) 15.2+2.4
Age at menarche (years) 11.4+1.4
Gynaecologic age 4.8+2.4
Admission haemoglobin (g/dl) 6.0+1.5
Urban Residence 50%
Weight status Normal weight (BMI <85%) 48
Overweight (BMI 85-95%) 18
Obese (BMI > 95%) 34
Gynaecological age < 2 years 30%
STI 12%
Mean age of 200 subjects was 15.2+2.4 years.
Mean hemoglobin level at admission 6.0+1.5 g/dl.
40% of patients were overweight / obese.
30% of patients had a gynaecological age of 2 years or
less.
PCOS accounted for 30% of admissions
Comparing the 60 subjects diagnosed with PCOS with the
60 subjects diagnosed with HPO axis immaturity, we found
a mean gynecological age of 62 months + 29.6 versus 15
months + 14.7 (p<0.001) respectively.
Figure 1: Etiology of AUB in adolescents admitted to Lalla ded
Hospital.
SA = Structural Abnormalities; OE = Other Endocrinopathies;
HPO = Hypothalamic-Pituitary-Ovarian
RESULTS
Ovulatory dysfunction related to PCOS accounted for 30%
of admissions and ovulatory dysfunction related to HPO axis
Int J Cur Res Rev | Vol 12 • Issue 10 • May 2020
7
Haq et.al: Etiology of abnormal uterine bleeding in adolescents – emphasis upon polycystic ovarian syndrome
immaturity accounted for next 30% of admissions, bleeding
disorders (primarily thrombocytopenia and Von Willebrand
disease) account for 14% of admissions. Endometritis 12%
was the fourth cause. This is in contrast to the findings in
most published studies of adolescents where bleeding dis-
orders account for 20% or more of the cases. Our disparate
finding is likely explained by the changing lifestyle, evolving
childhood obesity epidemic and the fact that our protocol al-
lowed for testing for hyperandro-genemia prior to treatment.
Table 2: Probability of etiology of AUB by initial
hemoglobin level at the time of the index hospital
admission (200)
Initial Hb level
(g/dl)
P-value
PCOS 6.2+0.2 NS
Other etiologies(60) 6.0+0.4
HPO axis immaturity 5.2+0.2 <0.05
Other etiologies(60) 6.2+0.4
Endometritis(24) 6.4+0.2 NS
Other etiologies 6.2+0.4
Bleeding disorders(28) 6.2+0.4 NS
Other etiologies 6.0+0.6
Other endocrinopathies(16) 6.0+0.6 NS
Other etiologies (60) 6.2+0.4
Structural abnormalities(12) 8.2+0.2 <0.001
Other etiologies 6.4+0.4
Comparisons of the etiologies of AUB by initial hemoglobin
level at hospital admission found that hemoglobin level was
significantly lower for adolescent subjects with HPO axis
immaturity(5.2g/dl) versus all other etiologies (6.2g/dl), p
<0.05.
Table 3: Probability of etiology of AUB by weight cat-
egory (n=200)
Overweight/
Obese
BMI>85%
Normal
weight
BMI <85%
P-value
PCOS (n=60) 75 25 <0.01
All other 45 55
HPO axis immaturity
(n=60)
50 50
NS
All other 63 37
Bleeding disorder
(n=28)
71 29
NS
All other 54 46
Endometritis(n=24) 50 50 NS
All other 56 44
Overweight/
Obese
BMI>85%
Normal
weight
BMI <85%
P-value
Other endocrinopa-
thies (n=16)
25 75
NS
All other 60 40
Structural abnor-
malities (n=12)
68 34
NS
All other 57 43
Comparison of six etiologies of AUB shown in above fig-
ure by weight category, overweight /obese versus normal
weight, found that girls with PCOS were significantly more
likely to be overweight /obese and those with Hypothalamic-
Pituitary-Ovarian HPO axis immaturity were more likely to
be normal weight than girls with all other etiologies of AUB.
We found that nearly three quarters of our adolescent sub-
jects with PCOS were overweight or obese, a significantly
higher proportion than all other etiologies of AUB.
DISCUSSION
Polycystic ovary syndrome (PCOS) was among common eti-
ology of AUB, accounting for 30% cases likely explained by
the shifting food habits and sedentary habit of the adolescent
population11, the evolving childhood obesity epidemic and
the fact that we followed protocol for testing hyperandrogen-
emia prior to hormonal treatment ofAUB12.
While bleeding disorders accounted for only 14% of cases.
Our finding is in opposite to many other studies where PCOS
is not reported as an etiology and bleeding disorders account
for 20% or more of the cases4-7.
In our study subjects with PCOS had a mean gynecologic
age of just over 5 years, well beyond the age associated with
physiologic ovulatory dysfunction, whereas subjects diag-
nosed with HPO axis maturity were well within the 2-3 year
accepted time frame with a mean gynecologic age of just
over 1 year.
Fifty percent of our subjects were from urban areas and hav-
ing high prevalence of PCOS and metabolic syndrome13, es-
pecially in conjunction with excess body weight. In a recent
study of 48 South Asian adolescents admitted to hospital in
India with AUB and severe anemia, 35% of the teens had a
BMI greater than 25 kg/m2 and 10/48 (21%) were found to
have PCOS14.
In our study nearly three-quarters of adolescent subjects with
PCOS were overweight or obese, a significantly higher pro-
portion than our subjects with all other etiologies of AUB.
Because of the serious comorbidities of PCOS, including
Table 3: (Continued)
Int J Cur Res Rev | Vol 12 • Issue 10 • May 2020 8
Haq et.al: Etiology of abnormal uterine bleeding in adolescents – emphasis upon polycystic ovarian syndrome
type 2 diabetes mellitus and cardiovascular disease15,16, it is
important to diagnose and treat this common endocrine dis-
order early. However, a barrier to early diagnosis of PCOS
in adolescents is the absence of specific diagnostic criteria,
as physiologic ovulatory dysfunction in the perimenarchal
period and multifollicular ovaries are normal findings.
Recommendations in the 2010 Consensus Statement from
the American Society for Reproductive Medicine/European
Society of Human Reproduction and Embryology for di-
agnosis of PCOS in adolescents include using biochemical
markers of hyperando-genemia as we did in this study, in-
stead of the non-specific clinical markers of hyperandrogen-
ism such as acne, hirsutism and alopecia17,18. However, there
is a lack evidence for ultrasonographic criteria for PCOS di-
agnosis in adolescents.
A prompt diagnosis of PCOS provides adolescents and their
parents with knowledge about the etiology of AUB, risk of
recurrence of AUB if treatment is discontinued, and preven-
tion of comorbidities. Thus making a diagnosis of PCOS as
the etiology for AUB allows for intensive intervention to as-
sist in improving the lifetime health of these adolescents.
We found that adolescent girls in our sample whose AUB
with severe anemia was related to ovulatory dysfunction
due to HPO axis immaturity had a significantly lower hemo-
globin level on admission to hospital than girls admitted
with all other etiologies of AUB. This is a surprising finding
and suggests to us that for perimenarchal girls whose rela-
tive inexperience in judging normal quantities of menstrual
blood loss coupled with embarrassment and reluctance to
bring attention to their menstrual bleeding likely delays their
presentation for needed health care and puts them at risk for
lifethreateninganemia19. We suggest that pediatricians and
other clinicians caring for perimenarchal girls document de-
tailed menstrual histories and monitor hemoglobin levels if
prolonged or frequent uterine bleeding is uncovered so that
treatment can be instituted prior to the development of se-
vere anemia and the necessity for hospital admission.
Another finding of this study that is different from older pub-
lished studies of adolescents admitted for AUB and severe
anemia is that 12% of the AUB episodes requiring hospitali-
zation in our subjects were related to endometritis. Studies
of adult women suggest that AUB secondary to infectious
endometritis is frequently underestimated20. In our sample of
adolescents, more than 20% were at risk for STIs because
they were sexually active. Infectious endometritis is a known
cause of AUB but unless a confidential sexual history, pelvic
examination, and tests for STIs are obtained the diagnosis
may be missed in adolescent girls and appropriate antibiotic
treatment may not be given.
Many adolescents are ambivalent about taking “birth con-
trol pills”, the treatment used to prevent recurrences which
is commonly seen. Cost utility analysis of screening for Von
Willebrand disease in women with menorrhagia was found
to be cost effective21, and we propose that screening ado-
lescent girls with AUB for PCOS as our protocol suggests
may also be cost effective. Finally our findings reaffirm the
importance of having a clinical protocol or guideline in or-
der to standardize practice and insure that girls with AUB
and severe anemia are tested for hyperandro-genemia before
treatment with hormones is begun and that those who are
sexually active are examined and tested for STIs22. The find-
ings of this study highlight the importance of considering
gynecologic age, ethnicity, weight status, and sexual activ-
ity when determining the etiology of AUB with severe ane-
mia in the adolescent population. For populations similar to
ours, were commend screening for biochemical markers of
hyperandro-genemia to aid in the diagnosis of PCOS prior
to beginning treatment with estrogens and/or progestins that
suppress ovarian androgens and preclude making the diag-
nosis. In addition, all adolescents with AUB and significant
anemia should have a confidential sexual history taken and
STIs should be considered in the etiology of AUB in adoles-
cents.
CONCLUSION
Abnormal Uterine Bleeding during adolescence is not always
associated with an ovulatory cause, thorough investigation
should be done and etiology ascertained. In our study we
found PCOS was a frequent endocrine mechanism of men-
strual disorder. Although most problems are explained by an
ovulation other causes must be considered and excluded in a
cost effective manner. Hormonal evaluation of these patients
is must and further management depends upon the cause.
LIMITATIONS
However a barrier to early diagnosis of PCOS in adoles-
cents is the absence of specific diagnostic criteria for this
age group, physiologic ovulatory dysfunction in the perime-
narchal period and observation that many adolescents have
multifollicular ovaries as a normal finding. A limitation of
this study is that it was performed in a single centre and pa-
tients were not followed up. Despite these limitations, this
study highlight the importance of considering gynecologic
age, residence, weight status and sexual activity when deter-
mining the etiology of AUB with severe anemia in the ado-
lescent population.
RECOMMENDATIONS
Pediatricians and other clinicians caring for perimenarchal
girls document detailed menstrual histories and monitor
hemoglobin levels if prolonged or frequent uterine bleed-
ing. Finally our findings reaffirm the importance of having
a protocol or guidelines in order to standardize practice and
ensure that girls with AUB and severe anemia are tested.
Int J Cur Res Rev | Vol 12 • Issue 10 • May 2020
9
Haq et.al: Etiology of abnormal uterine bleeding in adolescents – emphasis upon polycystic ovarian syndrome
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Article
2476 Poster Board II-453 Introduction It is unknown whether it is cost effective to screen adolescents with menorrhagia for von Willebrand disease (VWD) prior to starting oral contraceptive pills (OCPs). Because OCPs can mask a diagnosis of VWD, a woman is at risk for potential future traumatic or surgical bleeding, once OCPs are stopped. We, therefore, designed a decision analysis model to evaluate the cost utility of VWD testing in adolescents with menorrhagia. Methods A 20-year Markov decision analytic model was constructed to evaluate the cost-utility of two strategies: testing or not testing for VWD. The hypothetical patient is a 15-year-old female presenting with menorrhagia and a decision regarding VWD testing is made. The model includes probabilities of remaining well, suffering an acute menorrhagia bleeding event, surgical complications, OCP complications or dying. Probabilities, costs and utilities were estimated from published literature. The prevalence of type 1 VWD in adolescent females with menorrhagia was estimated to be 13%. We assumed all patients were treated with OCPs regardless of whether hemostatic testing was performed. All patients were assumed to have mild type I VWD, the most common subtype, and all were responsive to intravenous DDAVP. Probabilities of surgical complications in patients with and without VWD were based on adenotonsillectomy hemorrhage rates in children. The probability of acute menorrhagia bleeding necessitating hospitalization or red blood cell transfusion was estimated to be 1% in an adolescent with VWD and 0% in an adolescent with normal hemostatic testing. The sole complication from OCPs incorporated into this decision analytic model was acute deep vein thrombosis. Results The cost of testing adolescents with menorrhagia for VWD was 1,638,vs.1,638, vs. 1,251 for not testing for VWD. The effectiveness of not testing in quality-adjusted life-year (QALY) gained (14.237 QALY) was similar to the VWD testing strategy (14.246 QALY). Compared to not testing for VWD, screening for VWD had an incremental cost-effectiveness ratio (ICER) per QALY of 45,061/QALY,avaluetypicallyconsideredeconomicallyreasonable.Inonewaysensitivityanalysis,theoutcomeandICERweremostsensitivetotheprobabilitiesofanacutebleedingevent,surgicalcomplication,andtheprevalenceofVWD.MonteCarloprobabilisticsensitivityanalysis,substitutinginputdistributionsratherthanasinglepointestimatefortheprobabilities,costsandutilities,wasalsoperformed.Underthisassumption,testingforVWDisacosteffectivestrategyapproximately6045,061/QALY, a value typically considered economically reasonable. In one-way sensitivity analysis, the outcome and ICER were most sensitive to the probabilities of an acute bleeding event, surgical complication, and the prevalence of VWD. Monte Carlo probabilistic sensitivity analysis, substituting input distributions rather than a single point estimate for the probabilities, costs and utilities, was also performed. Under this assumption, testing for VWD is a cost-effective strategy approximately 60% of the time when the cost-effectiveness threshold is 100,000/QALY. Conclusions It is cost effective to perform VWD testing in adolescents presenting with menorrhagia prior to initiating OCPs. This is related to avoiding cost from postoperative and other bleeding when the diagnosis is masked by OCPs. Disclosures No relevant conflicts of interest to declare.
Article
Menstrual problems are known to be common amongst teenagers, but adequate recognition of the impact this may have on the adolescent and appropriate interventions that are focussed on the needs of the adolescents are limited. To date, the impact of menstrually related problems on the quality of life of adolescents has been poorly studied. Although some studies report on the impact of, in particular, dysmenorrhoea on school absenteeism, less is known about the impact on psychosocial functioning. For other menstrual problems, even less is known. It is increasingly recognized that understanding the impact on quality of life is an important measure to better understand the impact of the health problem and also to ensure the optimal delivery of patient-centred healthcare. This review will explore the current tools available for assessment of quality of life in adolescents and then focus on the specific menstrual problems (dysmenorrhoea, heavy menses, oligo/amenorrhoea) and what is known about their impact on the general well being of young women. Cultural differences in the presentation and impact of menstrual problems appear to be present with a greater impact on psychosocial functioning found with particularly oligo/amenorrhoea. There is clearly room for further study to explore and then optimize care.
Article
Objective: To investigate the prevalence of polycystic ovary syndrome (PCOS) in adolescents and its association with obesity. Design: Cross-sectional study using electronic medical records. Setting: Not applicable. Patient(s): Adolescents aged 15-19 years (n = 137,502). Intervention(s): None. Main outcome measure(s): PCOS diagnosed or defined according to National Institutes of Health (NIH) criteria. Result(s): The prevalence of a confirmed diagnosis of PCOS was 0.56%, which increased to 1.14% when undiagnosed cases with documented symptoms qualifying for PCOS according to NIH criteria were included. Compared with normal/underweight girls, the odds ratios (OR and 95% confidence interval [CI]) for confirmed PCOS diagnosis were 3.85 (3.04-4.88), 10.25 (8.16-12.84), and 23.10 (18.66-28.61) for overweight, moderately obese, and extremely obese adolescents, respectively, after adjusting for potential confounders. When adolescents with two or more supportive diagnoses were included (diagnosed and undiagnosed PCOS-NIH), the ORs (95% CI) for PCOS-NIH by weight class were significantly attenuated to 2.95 (2.53-3.44), 6.73 (5.78-7.83), and 14.65 (12.73-16.86) for overweight, moderately obese, and extremely obese adolescents, respectively. Conclusion(s): Overweight and obesity were associated with higher odds of PCOS in adolescents. Studies based solely on diagnosis codes may underestimate the prevalence of PCOS and overestimate the magnitude of the association between obesity and PCOS.
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Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age and is increasingly recognized as a disorder manifesting in the peripubertal and adolescent period. Diagnosis in the adolescent is difficult due to the high background rate of menstrual irregularity, the high prevalence of polycystic ovarian morphology and hyperandrogenic features in this population. Recent guidelines suggest that menstrual irregularity for over two years, reduced reliance on ultrasound diagnosis of polycystic ovarian morphology, and accurate assessment of hyperandrogenic and metabolic features are suitable strategies for the diagnosis of PCOS in the adolescent. Accurate diagnosis is important given the long-term implications of the disorder, with increasing emphasis on metabolic sequelae.
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Polycystic ovary syndrome (PCOS) is the most common endocrine problem affecting women of reproductive age and is investigated from many regions of the world. Some reports have indicated ethnic difference in its manifestation. This review addressed the evidences for ethnic variation in the expression of PCOS phenotypes and explored the potential ethnic-specific diagnosis of this syndrome. To determine ethnic variation, community prevalence and clinical and metabolic problems, including hyperandrogenism, oligomenorrhoea/amenorrhoea, polycystic ovaries, obesity, insulin resistance and the metabolic syndrome, had been compared from differing backgrounds and populations. Moreover, alink between ethnicity and variation in the metabolic phenotype of PCOS had also been identified. East Asian women with PCOS have a lower BMI and a milder hyperandrogenic phenotype, but with the highest prevalence of metabolic syndrome. South Asians in particular have a high prevalence of insulin resistance and metabolic syndrome, and are at risk for type 2 diabetes, with central obesity more than BMI reflecting their metabolic risk. African American and Hispanic women are more obese and more prone to metabolic problems. Besides, there is a higher prevalence of hirsutism among women of Middle Eastern and Mediterranean origin. Ethnically appropriate guidelines are needed for identifying anthropometric thresholds for better screening and diagnosis in high-risk ethnic groups.
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Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in females, with a high prevalence. The etiology of this heterogeneous condition remains obscure, and its phenotype expression varies. Two widely cited previous ESHRE/ASRM sponsored PCOS consensus workshops focused on diagnosis (published in 2004) and infertility management (published in 2008), respectively. The present third PCOS consensus report summarizes current knowledge and identifies knowledge gaps regarding various women's health aspects of PCOS. Relevant topics addressed-all dealt with in a systematic fashion-include adolescence, hirsutism and acne, contraception, menstrual cycle abnormalities, quality of life, ethnicity, pregnancy complications, long-term metabolic and cardiovascular health, and finally cancer risk. Additional, comprehensive background information is provided separately in an extended online publication.
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