Oleh : Nindya Meetasari Mega Maharani Ovy

Background
Obesity

PCOS

metabolic abnormalities including,

insulin resistance

increased dyslipidemia risk for type 2 diabetes.

Barker hypothesis
maternal nutritional constraints during pregnancy

adaptive responses in the fetus

limit growth

preferentially shunt nutritional resources to key organ systems

Decreased birthweight

relative thinness at birth

increasing

risk for developing obesity

cardiovascular disease

the metabolic syndrome

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 Other causes of testosterone (T) anovulation and greater than 58 ng/dl hyperandrogenemia or non-SHBG-bound were excluded by T (uT) greater than appropriate tests 15 ng/dl

Criteria for control (malefemale)

no personal history of hypertension and no personal or first-degree family history of diabetes normal glucose tolerance according to the World Health Organization criteria and additionally for female controls

no major medical or psychiatric illnesses

regular 27- to 35-d no clinical or menstrual cycles biochemical throughout their evidence of reproductive life 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 selfreported waist circumference was selfmeasured Hirsutism grading using the modified Ferriman Gallwey assessment

Additional phenotyping
transvaginal ultrasound

at least one ovary having a volume greater than 10 cm3 with no cysts or follicles more than 10mm in mean diameter

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

self-reported birthweight
normal low birthweight birthweight (<2500 g) (25004000 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

unknown based on inability to hyperandrogenic unaffected based measure T levels PCOS based on based on on normal T and due to elevated T levels elevated T levels DHEAS levels confounding and irregular medications, and regular and normal menses pregnancy, menstrual cycles menses 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 reproductive phenotypes in PCOS families

Women with PCOS Female relatives Male relatives

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

no significant associations between birthweight and any phenotype

Association of birthweight with metabolic parameters in PCOS families

No significant metabolic changes in relation to birthweight
no significant associations noted in either female or male relatives

PCOS probands Female and 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 selfreported.

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
AS & Europe 510% terjadi pada wanita usia reproduksi

Prevalence of PCOS

50% wanita dengan PCOS adalah obesitas

Penderita PCOS mempunyai resiko 7 kali lebih besar terkena infark miokardium

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

ANATOMI OVARIUM

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

FISIOLOGI OVARIUM
Ovulasi Pembentukan hormon sex steroid (estrogenprogesteron-androgen)

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, cushings 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- 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