MENSTRUAL CYCLE

PHYSIOLOGY AND PATHOPHYSIOLOGY

Dr. Supriyatiningsih, M.Kes, SpOG

Department of Obstetrics & Gynecology Faculty of Medicine Muhammadiyah University Yogyakarta Indonesia

THE NORMAL MENSTRUAL CYCLES IS DETERMINED BY A COMPLEX INTERACTION BETWEEN REPRODUCTIVE ENDOCRINE ORGAN

HYPOTHALAMUS ANTERIOR PITUITARY GLAND OVARY ENDOMETRIUM

But the main regulation is intraovarian

The Menstruation Cycle

3 activity during Menstrual Cycle : Hypothalamus and Pituitary activity Ovarian activity

Uterine activity

Environment CNS

Compartemen IV
Hypothalamus GnRH Compartemen III FSH Compartemen II Estrogen Compartemen I Ovary Progesterone

Anterior pituitary
LH

Uterus

Menses

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

Ovulasi

Number of oocytes at different ages

Age # of cells

3-6 weeks of gestation 8 weeks

8-20

20-40 weeks
Birth to puberty Reproductive years

Endoderm of the yolk sac Proliferation by mitosis Mitosis, meiosis, atresia 80% loss
Loss to atresia Ovulation

10,000
600,000 6-7,000,000

1-2,000,000
300,000 400-500

Membran sel LISOSOM Asam fosfatase Enzim litik

Penurunan aliran darah Vasokonstriksi a. spiralis

Prostaglandin

Iskemia

Upregulated MMP

Sekresi dan aktivasi sitokin

Makrofag PMN LImfosit granulasi

Menstruasi
Triptase & kimase
Regenerasi endometrium

Degranulasi

Sel Mast VEGF & FGF

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.

Definitions
Normal:
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

Term Amenorrhea Definition No uterine bleeding for at least 6 months Pattern

Menorrhagia

Excessive amount (>80 mL/cycle) or Occurs prolonged duration >7days, also called irregular hypermenorrhea intervals
Uterine bleeding occuring at irregular but irregular frequent interval, amount varies

at

Metrorrhagia

Menometrorrha Irregular, heavy, and prolonged menstrual irregular gi bleeding

Oligomenorrhe a

Decreased, scanty flow, the term Interval > 36-40 hypomenorrhea is used for regular timing days with scanty amount.
Interval days. <21

Polymenorrhea Regular, frequent menstruation Intermenstrual Bleeding periode or spotting between

normal Between periods (usually light flow)

Average blood loss with menstruation is 35-50cc.

95% of women lose <60cc.

Definitions
Menorrhagia: Prolonged > 7 days or > 80 cc occurring at regular intervals. Synonymous with hypermenorrhea

Menorrhagia occurs in 914% of healthy women.

Definitions Metrorrhagia:
Uterine bleeding occurring at irregular but frequent intervals.

Etiologies AUB
Organic Systemic Reproductive tract disease Iatrogenic Dysfunctional Ovulatory Anovulatory

Reproductive Tract Causes of Benign Origin

Atrophy Leiomyoma Polyps Cervical lesions Infection

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 Women

2.3/100,000 in 30-34 yr old 6.1/100,000 in 35-39 yr old 36/100,000 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

Kelainan
Organik
Sistemik Metabolik Keganasan Ggn kehamilan dini

Perdarahan dari uterus yang didasari oleh gangguan hormonal poros Hipotamus-hipofisis-ovarium semata, tanpa dijumpai kelainan organik, sistemik, metabolik, keganasan maupun gangguan 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 Rate
The 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 PMS

Women with PMS Symptom Behavioral Fatigue Irritability Labile mood with alternating sadness and anger Depression Oversensitivity Crying spells Social withdrawal Forgetfulness Difficulty concentrating Showing Symptoms (%) 92 91 81 80 69 65 65 56 47

Common Symptoms of PMS (Continued)

Physical Abdominal bloating Breast tenderness Acne Appetite changes and food cravings Swelling of the extremities Headache Gastrointestinal upset

90 85 71
70 67 60 48

Differences Between PMS and PMDD

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

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

Providers using these criteria Number of symptoms required

Obstetrician/gynec Psychiatrists, other ologists, primary mental health care care physicians providers One 5 of 11 symptoms

Differences Between PMS and PMDD (Continued)

Functional impairment Not required Interference with social or role functioning required Prospective daily charting of symptoms required for two cycles

Prospective charting of symptoms

Not required

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 symptomfree.

Differential Diagnosis
Psychiatric disorders Major depression Dysthymia Generalized anxiety Panic disorder Bipolar illness (mood irritability) Other Medical disorders Anemia Autoimmune disorders Hypothyroidism Diabetes Seizure disorders Endometriosis Chronic fatigue syndrome Collagen vascular disease

Differential Diagnosis (Continued)

Premenstrual exacerbation Of psychiatric disorders Of seizure disorders Of endocrine disorders Of cancer Of systemic lupus erythematosus Of anemia Of endometriosis Psychosocial spectrum Past history of sexual abuse Past, present, or current domestic violence

Diagnosis of PMS
PMS
A. 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 after C. Presence of one or more of the following symptoms Mild psychological discomfort Bloating and weight gain Breast tenderness Swelling of hands and feet Aches and pains Poor concentration Sleep disturbance Change 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 difficulties Marked lack of energy Marked change in appetite, overeating, or food cravings Hypersomnia or insomnia Feeling overwhelmed Other physical symptoms (e.g., breast tenderness, bloating, headache, joint or muscle pain)

Treatment of PMS

Oral contraceptives Vitamin B6 Bromocriptine Monoamine oxidase inhibitors Synthetic progestational agents Spironolactone Massage therapy Chiropractic therapy Calcium

MENOPAUSE

Irreguler menstruation

Gejolak panas

Osteoporosis
Tulang keropos Ngilu-ngilu Patah tulang Bungkuk Tambah pendek

NORMAL

Kerusakan bag tulang

The good news

Menopause and postmenopauseosteoporosis

Kulit keriput

Sukar tidur

Jantung berdebar

Pusing

Mudah pingsan

Gangguan fungsi seks

Vagina kering Hub. Seks sakit Lendir sedikit Nafsu sek turun

Libido menurun

Gangguan berkemih
Inkontinensia

Ngompol

Some benefits of estrogen replacement therapy (ERT) for treating menopausal related health problem
Estrogen 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) cholesterol
Nelson H. JAMA 2004;291:1610-20

Benefits of estrogen plus progestin in postmenopausal women

Estrogen + progestin Plasebo

WHI study. JAMA 2002;288:321-33

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

LIVER

ESTROGEN
HRT

KIDNEY

ADRENAL GLAND

Na+/ water retention (= weight gain) K+ elimination

Aldosterone
Increased edema
Increased body weight

Changes in body weight with Angeliq and estradiol alone

Mean weight change (kg) 1.5 1.0 0.5 0 0 -0.5 -1.0 -1.5 Angeliq (n = 224)
0 1 2 3 4 5 6 7

Estradiol (n = 225)
8 9 10 11 12 13

The end