ASSOCIATIONS OF BIRTHWEIGHT AND GESTATIONAL AGE WITH REPRODUCTIVE AND METABOLIC

PHENOTYPES IN WOMEN WITH POLYCYSTIC OVARIAN SYNDROME AND THEIR FIRST-DEGREE RELATIVES

Oleh :

Nindya Meetasari

Mega Maharani

Ovy

Background

metabolic abnormalities including,

insulin resistance dyslipidemiaincreased risk for type 2 diabetes.

PCOS

Obesity

Barker hypothesis

maternal nutritional constraints during pregnancy

adaptive responses in the fetus

preferentially shunt nutritional resources to key organ systems

limit growth

Decreased birthweight

relative thinness at birth

increasing

the metabolic syndrome

cardiovascular disease

risk for developing obesity

type 2 diabetes

Purpose

examine the relationship between birthweight and gestational age and its association with reproductive and metabolic phenotypes in women with PCOS and their first-degree relatives.

Subjects

Criteria for PCOS (NIH)

no more than six menses per year

either total testosterone (T) greater than 58 ng/dl or non-SHBG-bound T (uT) greater than 15

ng/dl

Other causes of anovulation and

hyperandrogenemia were excluded by appropriate tests

Criteria for control (male-female)

no major medical or psychiatric illnesses

no personal history

of hypertension

and no personal or first-degree

family history of diabetes

normal glucose

tolerance according to

the WorldHealth

Organization criteria and

additionally for female controls

regular 27- to 35-d menstrual

cycles throughout

their reproductive

life

no clinical or biochemical evidence of

hyperandrogenism

Study procedures

All subjects

completed a questionnaire capturing their medical and reproductive

history including

birthweight and gestational age

morning blood samples

obtained after an overnight

fast

Height and weight in the

subjects studied off-site

were self-reported

waist circumference

was self-measured

Hirsutism grading using the modified

Ferriman Gallwey

assessment

Additional phenotyping

at least one ovary having a volume greater than 10 cm3 with no cysts or

follicles more than 10mm in mean diameter

transvaginal ultrasound

Polycystic ovaries

Assays

Plasma glucose, insulin, FSH, T, uT, dehydroepiandrosterone

sulfate (DHEAS), SHBG, total cholesterol, high-density lipoprotein

(HDL), lowdensity lipoprotein (LDL), and triglyceride

Non-SHBG T was obtained from serum total T and non-SHBG fraction by ammonium sulfate precipitation,

Data analysisSpearman correlation coefficient strength of the relationship between self-reported birthweight and the medical record birthweight in PCOS families

self-reported birthweight

low birthweight (<2500 g)

normal birthweight

(2500–4000 g)

high birthweight(>4000 g)

 Analysis of covariance (ANCOVA) assess the relationship of birthweight with the continuous outcomes, such as metabolic parameters, adjusting for current subject age.

A generalized logits model the effect of birthweight on the reproductive phenotypes in sisters of probands, adjusting for current subject age

classified Sisters of probands

PCOS based on elevated T levels

and irregular menses

hyperandrogenic based on

elevated T levels and regular

menstrual cycles

unaffected based on normal T and DHEAS levels

and normal menses

unknown based on inability to

measure T levels due to

confounding medications, pregnancy,

menopause, hysterectomy, etc

Result

Birthweight validation Self-reported and actual birthweight

(Spearman correlation coefficient =0.81

95% CI, 0.66, 0.89;

P =0.001)

were highly correlated.

Association of birthweight with reproductivephenotypes in PCOS families

Women with PCOS

•no association of birthweight with reproductive parameters of the PCOS phenotype •P =0,42

Female relatives

•no significant associations

Male relatives

•no significant associations between birthweight and any phenotype

Association of birthweight with metabolic parameters in PCOS families

PCOS probands

•No significant metabolic changes in relation to birthweight

Female and male relatives

•no significant associations noted in either female or male relatives

Discussion

A study from England found associations of PCOS stigmata with length of gestation and birthweight.

the association high birthweight with hirsute women with polycystic ovaries who had higher than normal ovarian secretion of androgens

Another group in Spain has studied adolescent girls, primarily with premature pubarche, and has consistently found that low birthweight is associated with more severe reproductive and metabolic abnormalities.

Furthermore, these investigators have shown an inverse association between birthweight and ovarian volume

A large Finnish birth cohort study had findings consistent with this study, no relationship between birthweight andPCOSsymptoms.

We noted no other associations between birthweight and reproductive abnormalities in women with PCOS. 

limitations sample size: although large for the PCOS

literature, is relatively small from an epidemiological standpoint, and, therefore,

may lack the power to detect the more consistent associations between low birthweight and adverse cardiovascular risk.

Birthweight is just one biometric marker of the intrauterine milieu

birthweight and gestational age were self-reported.

conclusion birthweight, even corrected for gestational age, has

little substantive association with reproductive and metabolic abnormalities in women with PCOS and their relatives.

However, there are other intrauterine factors, for instance exposure to elevated androgen levels, that could contribute to a PCOS phenotype and not affect birthweight.

Finally, accelerated and excessive growth after birth has been found to be an additional risk factor for adult disease as well as PCOS stigmata.

Tinjauan pustaka

Introduction

Prevalence of PCOS

AS & Europe 5-10% terjadi pada

wanita usia reproduksi

Penderita PCOS mempunyai resiko 7 kali lebih besar

terkena infark miokardium

50% wanita dengan PCOS adalah obesitas

Definition

PCOS

A set of symptomps:

chronic anovulation, hyperandrogenism, and polycystic ovaries

associated with endocrine and metabolic disorders

without a primary disease in the pituitary or adrenal glands that underlies 

Ovarium terdiri dari :epitel, sel germinal, sel stroma & mesenkimal

ANATOMI OVARIUM

Ovulasi Pembentukan hormon sex steroid (estrogen-

progesteron-androgen)

FISIOLOGI OVARIUM

Patofisiologi

single defect in insulin action and secretion,

primary neuroendocrine defect, defects in androgen synthesis changes in the metabolism of cortisol

Diagnosis

clinical signs Hiperandrogenia jerawat, tumbuhnya rambut pada wajah,

leher serta abdomen. Perubahan tubuh menjadi tipe android dengan rasio waist to hip lebih dari 1.

Oligo ovulasi kurang dari delapan kali menstruasi per

tahun, dan menstruasinya seringkali terlewati selama beberapa bulan sekaligus, atau secara mudahnya mengalami amenore.

Obesity Lebih dari 65% wanita dengan SOPK

memiliki body mass index lebih dari 27. Distribusi lemak lebih banyak pada abdominal/visceral, yang berhubungan dengan kelainan metabolik seperti hipertensi, dislipidemia, resistensi insulin dan glukosa intolerans.

Sebagian besar berat badan normal sampai usia menarke dan kemudian mulai naik secara tajam pada usia 20 an.

laboratory signs

hormonal examination dehidroepiandrosteron sulfat (DHEAS) testoteron sex hormone binding protein. Glucose and insulin kolesterol total, LDL, HDL dan trigliserid

ultrasonografi

NIH

Diferential diagnosis

Adrenal lession: congenital adrenal hyperplasia, cushing’s syndrome, androgen secreting neoplasms

other pituitary or adrenal disorders hyperprolactinemia

MANAGEMENT• Lifestyle Modification• Diet• Exercise• bariatric surgery• Pil kontrasepsi oral kombinasi• Androgen receptor antagonist• 5-α Reduktase inhibitor• Clomiphene citrate• Insulin Sensitizing Agent• Gonadothropin dan GnRH analog• Combination of GnRH analogue and gonadotrophins• Laparoscopic ovarian surgery

Prognosis

Women who have this condition can get pregnant with the right surgical or medical treatments.

Pregnancies are usually normal.

complication

Increased risk of endometrial cancer Infertility (early treatment of polycystic

ovary disease can help prevent infertility or increase the chance of having a healthy pregnancy)

Obesity-related (BMI over 30 and waist circumferance greater than 35) conditions, such as high blood pressure, heart problems, and diabetes

Possible increased risk of breast cancer

TERIMAKASIH