MENSTRUAL CYCLEPHYSIOLOGY AND PATHOPHYSIOLOGYDr. Supriyatiningsih, M.Kes, SpOGDepartment of Obstetrics & Gynecology Faculty of Medicine Muhammadiyah University Yogyakarta Indonesia

THE NORMAL MENSTRUAL CYCLES IS DETERMINED BY A COMPLEX INTERACTION BETWEEN REPRODUCTIVE ENDOCRINE ORGANHYPOTHALAMUSANTERIOR PITUITARY GLANDOVARYENDOMETRIUM

But the main regulation is intraovarian

The Menstruation Cycle 3 activity during Menstrual Cycle :

Hypothalamus and Pituitary activity

Ovarian activity

Uterine activity

UterusMensesOvaryAnterior pituitaryHypothalamusCNSEnvironmentCompartemen ICompartemen IICompartemen IIICompartemen IVEstrogenProgesteroneFSHLHGnRH

To survive, the follicle must be exposed to a wave of gonadotropic hormone release

Ovulasi

Number of oocytes at different ages

Age# of cells3-6 weeks of gestationEndoderm of the yolk sac10,0008 weeksProliferation by mitosis600,0008-20Mitosis, meiosis, atresia6-7,000,00020-40 weeks80% loss1-2,000,000Birth to pubertyLoss to atresia300,000Reproductive yearsOvulation400-500

Membran selProstaglandinVEGF & FGFRegenerasi endometriumMenstruasi

Normal menstrual bleeding Occurs approximately once a month (every 26 to 35 days). Lasts a limited period of time (3 to 7 days). May be heavy for part of the period, but usually does not involve passage of clots. Often is preceded by menstrual cramps, bloating and breast tenderness, although not all women experience these premenstrual symptoms.

DefinitionsNormal:

Mean interval is 28 days +/- 7 days.Mean duration is 4 days.More than 7 days is abnormal.

Abnormal Bleeding

Abnormal bleeding (DUB or dysfunctional uterine bleeding) includes:Too frequent periods (more often than every 26 days). Heavy periods (with passage of large, egg-sized clots). Any bleeding at the wrong time, including spotting or pink-tinged vaginal discharge Any bleeding lasting longer than 7 days. Extremely light periods or no periods at all

Dysfunctional Uterine Bleeding (DUB)Most common menstrual disorder.Can affect any women from menarche to menopause.Often the first clinical diagnosis for any excessive menstrual bleedings.Diagnosis has to be confirmed by a process of exclusion of pathological causes.

Abnormal Uterine Bleeding: Terminology & Definitions

TermDefinitionPatternAmenorrheaNo uterine bleeding for at least 6 monthsMenorrhagiaExcessive amount (>80 mL/cycle) or prolonged duration >7days, also called hypermenorrheaOccurs at irregular intervalsMetrorrhagiaUterine bleeding occuring at irregular but frequent interval, amount variesirregularMenometrorrhagiIrregular, heavy, and prolonged menstrual bleedingirregularOligomenorrheaDecreased, scanty flow, the term hypomenorrhea is used for regular timing with scanty amount.Interval > 36-40 daysPolymenorrheaRegular, frequent menstruationInterval

Average blood loss with menstruation is 35-50cc.

95% of women lose

DefinitionsMenorrhagia:

Prolonged > 7 days or > 80 ccoccurring at regular intervals.Synonymous with hypermenorrhea

Menorrhagia occurs in 9-14% of healthy women.

DefinitionsMetrorrhagia:

Uterine bleeding occurring at irregular but frequent intervals.

Etiologies AUBOrganicSystemicReproductive tract diseaseIatrogenicDysfunctionalOvulatoryAnovulatory

Reproductive Tract Causes of Benign Origin AtrophyLeiomyomaPolypsCervical lesionsInfection

60% of women with PMB will be found to have atrophy. 10% will have polyps and 10% will have hyperplasia.Karlsson, et al., 1995

Incidence of Endometrial Cancer in Premenopausal Women2.3/100,000 in 30-34 yr old 6.1/100,000 in 35-39 yr old36/100,000 in 40-49 yr old

ACOG Practice Bulletin #14, 2000

DUB

Abnormal uterine bleeding for which an organic etiology has been excluded. It is either ovulatory or anovulatory in origin.

PUD Perdarahan dari uterus yang didasari oleh gangguan hormonal porosHipotamus-hipofisis-ovarium semata, tanpa dijumpai kelainan organik,sistemik, metabolik, keganasan maupun gangguan kehamilan dini -Kelainan Organik Sistemik Metabolik Keganasan Ggn kehamilan dini

Premenstrual Syndrome

Premenstrual Syndrome (PMS) is defined as the cyclic recurrence in the luteal phase of the menstrual cycle of a combination of distressing physical, psychological, and/or behavioral changes of sufficient severity to result in deterioration of interpersonal relationships and/or interference with normal activities. Nearly 200 symptoms have been associated with this definition and it is the clustering of these signs and symptoms that is the hallmark of PMS.

Catamenial

The term catamenial is derived from the Greek and signifies around menses. In general an instance where a single recognized medical condition presented in the premenstruum was referred to as a catamenial disorder while a cluster of symptoms was referred to as PMS.

Premenstrual Magnification

Many patients with psychiatric disorders also complain of worsening of their symptoms around the premenstrual phase, called premenstrual magnification (PMM).

PMS

Milder symptoms are believed to occur in about 30% to 80% of reproductive-age women, while severe symptoms are estimated to occur in 3% to 5% of menstruating women.

Concordance RateThe concordance rate (if both twins have PMS) was found to be significantly higher in monozygous twins (93%) than dizygous twins (44%) and in non-twin control women (31%).

Common Symptoms of PMSWomen with PMSSymptom Showing Symptoms (%)BehavioralFatigue92Irritability91Labile mood with alternating sadness and anger81Depression80Oversensitivity69Crying spells65Social withdrawal65Forgetfulness56Difficulty concentrating 47

Common Symptoms of PMS(Continued)PhysicalAbdominal bloating90Breast tenderness85Acne71Appetite changes and food cravings70Swelling of the extremities67Headache60Gastrointestinal upset48

Differences Between PMS and PMDD

Diagnostic criteria

Tenth Revision of the International Classification of Disease (ICD-10)

Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV)

Providers using these criteria

Obstetrician/gynecologists, primary care physicians

Psychiatrists, other mental health care providers

Number of symptoms required

One

5 of 11 symptoms

Differences Between PMS and PMDD(Continued)

Functional impairment

Prospective charting of symptoms

Not required

Not required

Interference with social or role functioning required

Prospective daily charting of symptoms required for two cycles

Patterns of PMS

Premenstrual symptoms can begin at ovulation with gradual worsening of symptoms during the luteal phase (pattern 1).

PMS can begin during the second week of the luteal phase (pattern 2).

Patterns of PMS(Continued)Some women experience a brief, time-limited episode of symptoms at ovulation, followed by symptom-free days and a recurrence of premenstrual symptoms late in the luteal phase (pattern 3).

The most severely affected women have symptoms that at ovulation worsen across the luteal phase and remit only after menses cease (pattern 4). These women describe having only one week a month that is symptom-free.

Differential DiagnosisPsychiatric disordersMajor depressionDysthymiaGeneralized anxietyPanic disorderBipolar illness (mood irritability)OtherMedical disordersAnemiaAutoimmune disordersHypothyroidismDiabetesSeizure disordersEndometriosisChronic fatigue syndromeCollagen vascular disease

Differential Diagnosis(Continued)Premenstrual exacerbationOf psychiatric disordersOf seizure disordersOf endocrine disordersOf cancerOf systemic lupus erythematosusOf anemiaOf endometriosisPsychosocial spectrumPast history of sexual abusePast, present, or current domestic violence

Diagnosis of PMSPMSA.Does not meet DSM-IV criteria but does meet ICD-10 criteria for PMS

B. Symptoms occur only in the luteal phase, peak shortly before menses, and cease with menstrual flow or soon afterC. Presence of one or more of the following symptomsMild psychological discomfortBloating and weight gainBreast tendernessSwelling of hands and feetAches and painsPoor concentrationSleep disturbanceChange in appetite

PMDD (DMS-IV Criteria)A.At least five of the symptoms below, with at least one being a core symptom, are present a week before menses and remit a few days after onset of menses:Depressed mood or dysphoria (core symptom)Anxiety or tension (core symptom)Affective lability (core symptom)Irritability (core symptom)Decreased interest in usual activities

PMDD (DMS-IV Criteria)(Continued)Concentration difficultiesMarked lack of energyMarked change in appetite, overeating, or food cravingsHypersomnia or insomniaFeeling overwhelmedOther physical symptoms (e.g., breast tenderness, bloating, headache, joint or muscle pain)

Treatment of PMS

Oral contraceptivesVitamin B6BromocriptineMonoamine oxidase inhibitorsSynthetic progestational agentsSpironolactoneMassage therapyChiropractic therapyCalcium

MENOPAUSE

Irreguler menstruation

Gejolak panas

OsteoporosisTulang keroposNgilu-ngiluPatah tulangBungkukTambah pendek

Kerusakan bag tulangNORMAL

The good newsMenopause and postmenopauseosteoporosis

Kulit keriput

Sukar tidur

Jantung berdebarPusingMudah pingsan

Gangguan fungsi seksVagina keringHub. Seks sakitLendir sedikitNafsu sek turun

Libido menurun

Gangguan berkemihInkontinensia Ngompol

Some benefits of estrogen replacement therapy (ERT) for treating menopausal related health problemEstrogen replacement therapy (ERT) results in the relief of menopausal symptoms such as hot flushes and atrophy of genital tract

ERT halts postmenopausal bone loss, increases bone mineral density (BMD) and reduces the incidence of fractures

ERT reduces levels of total cholesterol and low-density lipoprotein (LDL) cholesterolNelson H. JAMA 2004;291:1610-20

Benefits of estrogen plus progestin in postmenopausal women WHI study. JAMA 2002;288:321-33Estrogen + progestinPlasebo

Weight gain during traditional HRT has been one of the main reasons for discontinuation

Although it may not be the only reason, it contributes to poor compliance

Van Seumeren I. Maturitas 2000;34(Suppl 1):38

Renin substrate (= angiotensinogen)ReninAngiotensin IINa+/ water retention(= weight gain)K+ eliminationAldosteroneKIDNEYADRENAL GLANDLIVERESTROGENIncreased edemaIncreased body weight

Changes in body weight with Angeliq and estradiol alone1.51.00.500-0.50-1.5Mean weightchange (kg)Angeliq (n = 224)Estradiol (n = 225)12345678910111213-1.0

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