By I. Korda.. The menstrual cycle is a cycle of physiological changes that occurs in fertile...

By I. Korda.

The menstrual cycle is a cycle of physiological changes that occurs in fertile females.

The female menstrual cycle is determined by a complex interaction of hormones.

puberty is the process of physical changes by which a child's “body becomes an adult body capable of reproduction.

menarche - A woman's first menstruation is termed, and occurs typically around age 12. The menarche is one of the later stages of puberty in girls.

menopause - the end of a woman's reproductive phase, which commonly occurs somewhere between the ages of 45 and 55. Climacteric: 47-55 years

Premenopause: 5 years before Postmenopause starts 1 year after menopause

Perimenopause: transitional phase between pre- and postmenopause: 2 years before and 1 year after

Menstrual cycle:

Days 1-5: Estrogen Falls, FSH Rises.

Menstrual bleeding begins on Day 1 of the cycle and lasts approximately 5 days. During the last few days prior to Day 1, a sharp fall in the levels of estrogen and progesterone signals the uterus that pregnancy has not occurred during this cycle. This signal results in a shedding of the endometrial lining of the uterus.

Since high levels of estrogen suppress the secretion of FSH, the drop in estrogen now permits the level of follicle stimulating hormone (FSH) to rise.

FSH stimulates follicle development.

By Day 5 to 7 of the cycle, one of these follicles responds to FSH stimulation more than the others and becomes dominant. As it does so, it begins secreting large amounts of estrogen.

Days 6-14: Estrogen Is Secreted, FSH Falls.

Estrogen is secreted by the follicle during this phase of the menstrual cycle. It

stimulates the endometrial lining of the uterus

suppresses the further secretion of FSH.

At about mid-cycle (Day 14), the estrogen helps stimulate a large and sudden release of luteinizing hormone (LH).

This LH surge, which is accompanied by a transient rise in body temperature, is a sign that ovulation is about to happen.

The LH surge causes the follicle to rupture and expel the egg into the Fallopian tube.

Days 14-28: Estrogen And Progesterone Secretion First Rise, then Fall.

After rupture of the follicle, it is transformed into the corpus luteum and produces progesterone.

P supports to prepare the endometrial lining for implantation of the fertilized egg.

(If the egg is fertilized, a small amount of human chorionic gonadotrophin (hCG) is released that stimulates further progesterone production.)

After implantation, the trophoblast will secrete human Chorionic Gonadotropin (hCG) into the maternal circulation.

HCG keeps the corpus luteum viable.The corpus luteum continues to produce estrogen and progesterone, which keep the endometrial lining intact.

By about week 6 to 8 of gestation, the newly formed placenta takes over the secretion of progesterone.

If the egg is not fertilized, the corpus luteum shrinks, and the levels of estrogen and progesterone drop, the uterus sheds its lining, and menstruation begins.

Normal Menses:Flow lasts 2-7 daysCycle 21-35 days in

lengthTotal menstrual blood

loss 20-60 mLThe menstruation must

be regular, painless.

In addition, with no estrogen to suppress it, FSH levels again start to rise. Thus, one cycle ends and another begins.

Estrogens

Estrogens stand for a group of hormones: Estradiol (approximately 10-20% of circulating estrogens) Estrone (approximately 10-20% of circulating estrogens) Estriol (approximately 60-80% of circulating estrogens)

Estradiol is produced by the ovaries. It is the primary circulating estrogen before menopause. It is also the strongest estrogen and is responsible to the monthly ovulation and normal menstrual cycles.

Estrone is produced by the fatty tissues. It is less potent than estradiol, but more important after the menopause

Estriol is an estrogen that is prominent mostly during pregnancy.

ProgesteroneProgesterone is made by the adrenal glands in both sexes and by the testes in males. It is a precursor of testosterone and of all the important adrenal cortical hormones.

Progesterone is made from the sterol pregnenolone that derives from cholesterol,

Progesterone stimulates the growth of a endometrial lining, prepares breast tissue for the secretion of breast milk, and generally maintains the advancement of pregnancy.

AndrogensAndrogens stands for a group of primarily male hormones:

testosterone androstenedione dehydroepiandrosterone).

Androgens are also produced in the ovaries.

Menstrual cycle irregularities:Menstrual cycle irregularities:1. abnormal frequency1. abnormal frequency

Kaltenbach chart:

Normal cycle

Abnormal frequency:oligomenorrhea

Abnormal frequency:polymenorrhea

Duration: 28 d 5Amount: 3-5 pads or tampons (35 mL)

Duration > 35 days

Duration < 22 days

Menstrual cycle irregularities:Menstrual cycle irregularities: 2. abnormal amount of duration 2. abnormal amount of duration

Kaltenbach chart:

Normal cycleDuration: 28 d 5Amount: 3-5 pads or tampons 35 mL)

Hypomenorrhea

Hypermenorrhea

Menorhagia

Amount < 2 per day

Amount > 5 per day

Duration 7-14 daysat regular intervals

Menstrual cycle irregularities:Menstrual cycle irregularities:3. others3. others

Spotting: bleeding unrelated to menses

Ovulatory bleeding

Metrorrhagia: > 14 days, no clear cycle

Painful menses:Algomenorrhea — pain during menses in genital

organs region Dysmenorrhea — general disturbances during

menses (headache, nausea, anorexia, raised irritability)

Algodysmenorrhea — a combination of local pain and general state disturbance

Amenorrhea: absence of bleeding for more than 6

months

Primary amenorrhea is the absence of menstrual function from puberty age.

Secondary amenorrhea is the suppression of menstrual function in woman who has menstruated before.

Clinical Presentation Clinical Presentation Physical examination Physical examination

Height and Weight Height and Weight Sign of thyroid disease Sign of thyroid disease Secondary sexual characteristics Secondary sexual characteristics

ThelarcheThelarche AdrenarcheAdrenarche

Decrease in breast size or Vaginal dryness Decrease in breast size or Vaginal dryness Presence of Cervix and Uterus Presence of Cervix and Uterus

Differential Diagnosis Differential Diagnosis Primary amenorrhea

Gonadal failure Anorexia nervosa

Secondary amenorrhea Hypothalamic disorders and PCOD

- 4962%Pituitary - 7 16 % Ovarian disorder 10% Ascherman’s syndrome

7%

Physiologic Amenorr Physiologic Amenorrheahea

PregnancyLactation

Menopause

HormoneHormone : contraception etc. : contraception etc.

Dysorder of Dysorder of HypothalamusHypothalamus

Abnormalities Affecting Release of Abnormalities Affecting Release of- Gonadotropin Releasing Hormone- Gonadotropin Releasing Hormone

Variable Estrogen Status Anorexia nervosa -Exercise induced -Stress inducedPseudocyesisMalnutrition Chronic diseases :

DM, Renal, Lung, Liver, Chronic infection, Addison’s disease

Hyperprolactinemia Thyroid dysfunction

Euestrogenic StatesObesityHyperandrogenism

PCOD Cushing’s syndrome Congenital adrenal hype

rplasia Androgen secreting adre

nal tumor Androgen secreting ovar

ian tumor

Granulosa cell tumoridiopatic

Menstrual disordersMenstrual disordersIrregular patterns of bleedingHypothalamic ovarian insufficiency:

Psychogenic stress, anorexia nervosaPituitary causes:

for instance: acromegaly – increased somatotropic hormones (STH) Cushings diseas: impaired cortisol rhythm

Ovary: polycystic ovaryThyroid: hypothyroidism: anovulatory

cylces and dysfunctional bleeding

hyperthyroidism: hypomenorrhea/ oligomenorrhea

Adrenal: Cushings syndrome: impaired cortisol rhythm

Polycystic Ovary Syndrome Polycystic Ovary Syndrome (PCOS)(PCOS)

The ovaries contain many small follicles or cysts. Each has an egg, but they do not grow normally and shrink before ovulation. Each month, new follicles develop and shrink into cysts.

The fertility is reduced.

Most PCOS cases are unexplained.

• The disorder may be inherited.

• Deficiency in luteinizing hormone (LH)

• Resistance to insulin. A similar effect on the ovaries can occur in women with eating disorders (anorexia or bulimia), or women whose bodies do not properly make estrogen and other steroids (for example, women with congenital adrenal hyperplasia).

Polycystic Ovar Polycystic Ovaryy SyndromeSyndrome (PC (PCOOSS))

Clinical consequences of

persistent anovulation

1 . Infertility

2. Menstrual dysfuncti on

3 . Hirsutism, Alopec AAAA,

4 . Riskofendometri alcancer ,breast cancAA

5 . RiskofCVSdiseasA

6 . RiskofDMin patiAAAA AAAA AAAAAAA Aesi stance

Disorder of Anterior Pituitary

Pituitary Tumors Non functioning adenomas - Hormone secreting adeno

ma Prolactinoma Cushing’s disease Acromegaly Primary hyperthyroidism

CraniopharyngiomaMeningiomaGlioma

Infarction Surgical or Radi ological ablatio

n Sheehan’s synd

rome Diabetic vasculi

tis

Prolactin Secreting Adeno Prolactin Secreting Adenomama

Most common pituit ary tumor

50% identified at autopsy

Disruption of the rep roductive mechanis

mS/S PRL

Amenorrhea- Visual field defect

Galactorrhea-A AAAAAAA

Treatment Medical : dopamine a

gonistSurgical

Sheehan’s syndrome Sheehan’s syndrome Postpartum hemorrhag

e Acute infar ction and ne

crosis Hypopituitarism= earl

y in the PP period Failure of lactation Loss of pubic and axilla

ry hair Deficiencies :

GH, Gn (FSH,LH), ACTH, TSH (in frequency)

Disorders of the Ovar Disorders of the Ovaryy

1. Chromosomal etiolog 1. Chromosomal etiologyyTurnerTurner’s’s Syndrome SyndromeMosaicismMosaicism XY gonadal dysgenesis XY gonadal dysgenesis Gonadal agenesis Gonadal agenesis

2 . Resistance ovarian syn 2 . Resistance ovarian synAAAA A AAAA A ( ) ( )

3. Premature ovarian fai 3. Premature ovarian faiAAAA AAAA

(the early depletion of (the early depletion of AAAAAAAAAA) AAAAAAAAAA)

4. Iatrogenic causes: AAAAAA AA AAAAAAAAA AAA AAAAAAAAr apy

5 . Infections 6 . Autoimmune

di sor der s 7 . Galactosemia 8 . Cigarette sm

AAAAA 9 . Idiopathic

Turner’s Syndrome Gonadal dysgenesis associated with 4

5,XO Most commonchromosomal abnormal i t

y i nspontaneous aborti onCharacteri sti cs

AAAAAA AAAAAAAAAAA -AAAA AAA A AA

Short stature Autoi mmuneA AAAAA AAAA CVSanomal i es

cubitus valgus Renal anomal i es

Mosai ci smAAAAAA AAA

Ovarian Causes Ovarian Causes Premature ovarian failur

e follicular depletion before age40

aut oi mmune di seasesgenet i csi nf ect i ous physicali nsul t :

Rad.Chemo.

Investigation: Laparotomy ? Aut oi mmune di sease

A AAAAAA A AAAAAAAAA AAAAAAA A

Primordial follicles f ail to progress

Despite elevated gonadotropins

Normal growth anddevelopement

Disorders of the Disorders of the OO utflow utflow TT ract or ract or UUterusterus

1. Asherman’s syndrome 2. Mullerian anomalies 3. Androgen Insensitivity

( F)4. Infection TB

1. Asherman’s Syndrome

Cause : Curettage,

Uterine surgery Diagnosis :

HSGHysteroscope

/ : Miscarriage

DysmenorrheaHypomenorrhea

2. Mullerian anomalies 2. Mullerian anomalies

AAAA AA A AAAAAAAA A AAAAAAA AAA

Ovaries : Normal Associ at ed anomal

i esurinaryskeleton

Investigation : U/S , MRI, Laparos

cope ?

- - - Mayer Rokitansky Kuster Hauser syndr- - - Mayer Rokitansky Kuster Hauser syndromeome

Mullerian AgenesisMullerian Agenesis

ImperforatImperforatee HHymensymens

3. Androgen Insensitivity 3. Androgen Insensitivity ( ( FF))

Male Pseudohermaphrodite

Gonadal Sex :46xy Phenotype Female

Blind vaginal canal Uterus absent Absent or meager pubic and a

xillary hair Malignancy, Hormone :

T or slightly LH

Premenstrual Syndrome

Case20 year old Jessica

Episodes of irritability and moodiness

Lead to huge arguments with her boyfriend.

Sleeps away the day and miss school or work

Her boyfriend jokes and makes off-the-wall remarks about PMS. She comes to you for advice.

Bloated, tired and hungry during the days just prior to menses.

DefinitionsPMS = Recurrent psychological or physical

symptoms during the luteal phase of menstrual cycle, resolves by the end of menstruation, and interferes with some aspect of function.

Premenstrual Dysphoric Disorder (PMDD) = more severe form of PMS meeting DSM-IV criteria.

About three per cent of women across all countries suffered the most severe type of PMS, called premenstrual dysphoric disorder (PMDD)

Symptoms

Anger Outbursts

Symptoms

Cravings

Irritability

Mood Lability

Symptoms of PMSBehavioral

Mood lability (81)Food cravings (78)Increased appetite

(70)Oversensitivity

(69)Anger (67)Crying easily (65)Feeling isolated

(65)

Psychological

Irritability (91) Fatigue (92)Anxiety/tension

(89)Depression

(80)Forgetfulness

(56)Poor

concentration (47)

Physical

Fatigue (92)Bloating (90)Breast

tenderness (85)Acne (71)Swelling (67)Headache (60)GI symptoms

(48)Hot flashes (18)Heart

palpitations (14)

Dizziness (14)

Diagnosing PMSUCSD criteria:

>1 somatic and affective symptom 5 days prior to menses x 3 cycles Somatic: Depression, anger, irritability, confusion, social

withdrawal, fatigue Affective: breast tenderness, bloating, headache, swelling

Resolve within 4 days onset of menses and symptom free until day 12 of cycle

Not due to medications, drugs or ETOH useCauses Dysfunction

Marital, parenting, work/school attendance/performance, isolation, legal difficulties, suicidal ideation

Differential DiagnosisMenstrual exacerbation of:

psychiatric disorderMedical condition:

Dysmenorrheahyper- or hypo- thyroidismPeri-menopauseMigraineChronic fatigue syndromeIrritable bowel syndrome

Rx of mild to moderate PMS

Some evidence:Vit B6 during luteal phase (1 system review)

neurotoxicityCalcium (2 large RCTs )

Benefits bonesEvening primrose oil (weak RCTs)Magnesium (weak RCTs)

Unknown benefit:Exercise – shown to be associated with less severe

symptoms (no RCTs)Relaxation – limited evidence (one RCT)Chiropractic manipulation – insignificant effect (weak

crossover trial)CBT (weak RCTs) – insufficient evidenceLight therapy – no significant effect (one small RCT)Eliminating caffeine (small trials, expert opinion)Reducing sugar and salt (expert opinion)Beneficial:

Spirolactone 500-200 mg OD during luteal phase (RCTs)

Relieves breast tenderness, weight gain, mood Contraindicated if pregnant

Likely beneficial:Alprazolam 0.25-1 mg TID in luteal phase (RCTs)

DependenceBuspirone 5-10 mg TID (one RCT)

global symptom improvementGnRH analogues (one systematic review)

Short term Rx only. Considered in patients not responding to other therapies 11% Bone loss with continuous Rx should not exceed 6

months without add-back hormone therapy Hot flashes, nausea, night sweats, headaches Given in luteal phase improves breast tenderness

Metolazone (one RCT) Improved weight gain, mood, swelling

NSAIDs in luteal phase (RCTs)OCP (RCTs)

Improved acne, appetite, food cravings

Rx of moderate to severe PMS

Trade-off between benefit and harmClompramine (RCTs)

Improved psychological symptoms only Significant drowsiness, nausea, vertigo, headache

Danazol 200 mg OD (RCTs) Effective but masculinization

SSRIs (one systemic review, RCTs) Effective but may increase risk of suicide Warnings about use in children and adolescents

Progesterone (systemic reviews) Contradictive studies Bleeding, dysmenorrhea, abdo pain, nausea, headache

Approach

Hx – regularity of cycle, timing of symptoms in cycle, severity and type of dysfunction

PE – aimed at R/O medical and psychiatric causesINV – CBC, lytes, TSH, +/- menopause workupCalendar of Premenstrual Experiences (COPE)Re-assess: ? meets diagnostic criteriaIf symptom-free in follicular and

not severely impaired: Conservative management is first line

Severely impaired: Pharmacological management is first line

If not-symptoms-free in follicular phase considerExacerbation of medical or psychiatric disorder

SummaryBegin and end of reproductive period varies

between different societies.Menstrual cycle irregularities and disorders

are frequent (3-30%) and can be determined with standardized charts.

Events of/in the reproductive period, such as age at menarche, irregularities, age at menopause, etc. are markers for increased risk for health outcomes in later life.

Thank you for your attention!