by i. korda.. the menstrual cycle is a cycle of physiological changes that occurs in fertile...
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By I. Korda.
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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.
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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
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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.
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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.
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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.
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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.)
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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.
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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.
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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.
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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.
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AndrogensAndrogens stands for a group of primarily male hormones:
testosterone androstenedione dehydroepiandrosterone).
Androgens are also produced in the ovaries.
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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
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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
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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
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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.
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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
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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%
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Physiologic Amenorr Physiologic Amenorrheahea
PregnancyLactation
Menopause
HormoneHormone : contraception etc. : contraception etc.
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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
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Euestrogenic StatesObesityHyperandrogenism
PCOD Cushing’s syndrome Congenital adrenal hype
rplasia Androgen secreting adre
nal tumor Androgen secreting ovar
ian tumor
Granulosa cell tumoridiopatic
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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
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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).
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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
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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
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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
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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)
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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
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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
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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
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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
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1. Asherman’s Syndrome
Cause : Curettage,
Uterine surgery Diagnosis :
HSGHysteroscope
/ : Miscarriage
DysmenorrheaHypomenorrhea
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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 ?
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- - - Mayer Rokitansky Kuster Hauser syndr- - - Mayer Rokitansky Kuster Hauser syndromeome
Mullerian AgenesisMullerian Agenesis
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ImperforatImperforatee HHymensymens
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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
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Premenstrual Syndrome
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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.
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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)
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Symptoms
Anger Outbursts
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Symptoms
Cravings
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Irritability
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Mood Lability
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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)
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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
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Differential DiagnosisMenstrual exacerbation of:
psychiatric disorderMedical condition:
Dysmenorrheahyper- or hypo- thyroidismPeri-menopauseMigraineChronic fatigue syndromeIrritable bowel syndrome
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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)
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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
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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
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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
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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
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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.
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Thank you for your attention!