Dr. Mohammed AbdallaDr. Mohammed Abdalla
ASSESSMENT OF A CASEASSESSMENT OF A CASE
OFOF AMENORRHEAAMENORRHEA
AMENORRHEAAMENORRHEA
Amenorrhea is the absenceAmenorrhea is the absence
or abnormal cessation ofor abnormal cessation of
m...
Primary amenorrhea
is defined either as absence of menses by
age 14 years with the absence of growth
or development of se...
Secondary amenorrhea
is defined as the cessation of
menstruation for at least 6 months
or for at least 3 of the previous ...
PHYSIOLOGY
Circulating estradiol stimulates growth of the
endometrium. Progesterone, produced by
the corpus luteum formed ...
the age of the first menses varies by
geographic location, as demonstrated by a
World Health Organization study
comparing ...
The number of primordial follicles in the
human ovary peaks during the fifth
gestational month at approximately 7
million....
by age 20 years, women have established
regular and persistent patterns of menstrual
cycle length with little variation .
...
 In the first year after menarche, the fifth
percentile for menstrual cycle length is 23 days
and the 95th percentile is ...
How common is it?
• Secondary amenorrhoea (prevalence about 3%)
• primary amenorrhoea (prevalence about 0.3%)
• Between 10...
Etiology ofEtiology of PRIMARY
amenorrhoea
Secondary sexual
characteristics present
• Pregnancy
• Constitutional delay
• Genito-urinary malformation, e.g. imperforat...
Secondary sexual
characteristics absent
• Hypothalamic dysfunction, e.g. chronic illness, anorexia,
weight loss, 'stress'
...
Ambiguous external genitalia
• Congenital adrenal hyperplasia
• Androgen-secreting tumour
• 5-Alpha-reductase deficiency
Turner's syndrome
• Turner's syndrome is caused by either a
complete absence or a partial abnormality of
one of the two X ...
Constitutional delay
• In this condition there is no anatomical
abnormality and endocrine
investigations show normal resul...
Androgen insensitivity syndrome
(AIS)
 formerly known as testicular feminization,
 46XY
 failure of normal masculinizat...
5-alpha-reductase deficiency
(5-ARD)
 inability to convert testosterone to the more
physiologically active dihydrotestost...
Measuring the clitoris is an effective method
for determining the degree of androgen
effect. The clitoral index can be det...
Imperforate hymen
 Imperforate hymen represents the most common and
most distal form of vaginal outflow obstruction.
 Cl...
Imperforate hymen
Etiology ofEtiology of secondary
amenorrhoea
No features of androgen excess present
• Physiological, e.g. pregnancy, lactation, menopause
• Iatrogenic, e.g. depot medr...
Features of androgen excess present
• Polycystic ovary syndrome
• Cushing's syndrome
• Late-onset congenital adrenal hyper...
Polycystic ovary syndrome
• This condition is characterized by hirsutism, acne,
alopecia, infertility, obesity, and menstr...
• Menopause/ovarian failure occurring before the
age of 40 years is considered premature.
• Auto-immune disease is the mos...
Ovarian failure (premature
menopause(
chromosomal
anomalies
autoimmune
disease
If the woman is under 30, a
karyotype shoul...
autoimmune related dysfunction
 The most common association is with thyroidThe most common association is with thyroid
di...
Hyperprolactinaemia
• A prolactinoma is the commonest cause of
hyperprolactinaemia (60% of cases).
• Other causes include ...
Weight-related amenorrhoea
• A regular menstrual cycle is unlikely to
occur if the body mass index (BMI) is less
than 19 (...
Post-pill' amenorrhoea
• This is defined as absence of menstruation
for 6 months following cessation of the
combined oral ...
Progestogen-associated amenorrhoea
• Depot medroxyprogesterone acetate inhibits the secretion of
gonadotrophins and thus s...
ASSESSMENT of primaryASSESSMENT of primary
amenorrheaamenorrhea
TSH elevated
hypothyroidism
Normal
bone age
delayed
constitutional delay
Normal
LH, FSH, and prolactin levels
elevated
kar...
If the pregnancy test result is negative
TSH and prolactin levels
progestin challenge
within reference range
consider anov...
genital tract
abnormalities
karyotype
If the karyotype is 46,XY If the karyotype is 46,XX
testosterone levels
male range f...
Breast development, pubertal growth spurt,
and adrenarche are delayed or
absent in persons with
hypothalamic pituitary
fai...
adrenarche occurs normally, while
estrogen-dependent breast development and the
pubertal growth spurt are absent or delaye...
Secondary AmenorrheaSecondary Amenorrhea
HistoryHistory
A good history can reveal the etiologicA good history can reveal the etiologic
diagnosis in up to 85% of ca...
If the history and physicalIf the history and physical
exam are suggestive of aexam are suggestive of a
certain etiologyce...
In patients that will not demonstrate anyIn patients that will not demonstrate any
obvious etiology for their amenorrheaob...
How do I assess my patient with
secondary amenorrhoea?
• Risk of pregnancy
• Associated symptoms, e.g. galactorrhoea, hirs...
• Height and weight: calculate body mass index if appropriate.
• Signs of excess androgens, e.g. hirsutism, acne
• Signs o...
Preg.test
TSH ,PROLACTIN’,
Prog.challenge test
withdrawal
bleeding
without withdrawal
bleeding
hypoestrogenic compromised
...
•Raised testosterone/androgen level. This group includes women with
polycystic ovary syndrome (mildly raised level), and w...
Complications and prognosis
• Osteoporosis: women with amenorrhoea associated with oestrogen
deficiency are at significant...
• Endometrial hyperplasia: women with amenorrhoea but
no associated oestrogen deficiency are at increased risk of
endometr...
Thank youThank you
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  1. 1. Dr. Mohammed AbdallaDr. Mohammed Abdalla ASSESSMENT OF A CASEASSESSMENT OF A CASE OFOF AMENORRHEAAMENORRHEA
  2. 2. AMENORRHEAAMENORRHEA Amenorrhea is the absenceAmenorrhea is the absence or abnormal cessation ofor abnormal cessation of menstruation.menstruation.
  3. 3. Primary amenorrhea is defined either as absence of menses by age 14 years with the absence of growth or development of secondary sexual characteristics .  OR as absence of menses by age 16 years with normal development of secondary sexual characteristics.
  4. 4. Secondary amenorrhea is defined as the cessation of menstruation for at least 6 months or for at least 3 of the previous 3 cycle intervals.
  5. 5. PHYSIOLOGY Circulating estradiol stimulates growth of the endometrium. Progesterone, produced by the corpus luteum formed after ovulation, transforms proliferating endometrium into secretory endometrium. If pregnancy does not occur, this secretory endometrium breaks down and sheds as a menstrual blood.
  6. 6. the age of the first menses varies by geographic location, as demonstrated by a World Health Organization study comparing 11 countries, which reported a median age of menarche of 13-16 years across centers. PHYSIOLOGY
  7. 7. The number of primordial follicles in the human ovary peaks during the fifth gestational month at approximately 7 million. After this initial pool is in place, no additional primordial follicles are formed. In some cases, loss of menstrual regularity is an early sign of declining fertility and impending premature ovarian failure PHYSIOLOGY
  8. 8. by age 20 years, women have established regular and persistent patterns of menstrual cycle length with little variation . on an individual basis Relatively stable and predictable menstrual cycle length continues until age 40 years. PHYSIOLOGY
  9. 9.  In the first year after menarche, the fifth percentile for menstrual cycle length is 23 days and the 95th percentile is 90 days.  By the fourth year after menarche, the 95th percentile for cycle length has declined from 90 days to approximately 50 days.  by 7 years after menarche, cycles are more stable; the fifth percentile in cycle length is 27 days, and the 95th percentile is 38 days. PHYSIOLOGY
  10. 10. How common is it? • Secondary amenorrhoea (prevalence about 3%) • primary amenorrhoea (prevalence about 0.3%) • Between 10 and 20% of women complaining of infertility have amenorrhoea [Franks, 1987]. • Up to 50% of competitive runners (training 80 miles per week) and up to 44% of ballet dancers have amenorrhoea [Balen, 1999a].
  11. 11. Etiology ofEtiology of PRIMARY amenorrhoea
  12. 12. Secondary sexual characteristics present • Pregnancy • Constitutional delay • Genito-urinary malformation, e.g. imperforate hymen, transverse vaginal septum, absent vagina with or without a functioning uterus • Androgen insensitivity: XY female or testicular feminization • Resistant ovary syndrome
  13. 13. Secondary sexual characteristics absent • Hypothalamic dysfunction, e.g. chronic illness, anorexia, weight loss, 'stress' • Gonadotrophin deficiency, e.g. Kallman's syndrome • Hydrocephalus • Tumours of the hypothalamus or pituitary • Hypopituitarism • Hyperprolactinaemia • Gonadal failure, e.g. ovarian dysgenesis/agenesis, premature ovarian failure • Hypothyroidism
  14. 14. Ambiguous external genitalia • Congenital adrenal hyperplasia • Androgen-secreting tumour • 5-Alpha-reductase deficiency
  15. 15. Turner's syndrome • Turner's syndrome is caused by either a complete absence or a partial abnormality of one of the two X chromosomes. About 50% have mosaic forms such as 45X/46XX or 45X/46XY. • Features :( short stature, web neck, lymphoedema, shield chest with widely spaced nipples, scoliosis, wide carrying angle, coarctation of the aorta, and streak ovaries.)
  16. 16. Constitutional delay • In this condition there is no anatomical abnormality and endocrine investigations show normal results. • It is caused by immature Pulsatile release of gonadotrophin-releasing hormone; maturation eventually occurs spontaneously.
  17. 17. Androgen insensitivity syndrome (AIS)  formerly known as testicular feminization,  46XY  failure of normal masculinization of the external genitalia in chromosomally male individuals. This failure of virilization can be either complete (CAIS) or partial (PAIS), depending on the amount of residual receptor function.  affected individuals have normal testes with normal production of testosterone and normal conversion to dihydrotestosterone (DHT), which differentiates this condition from 5-alpha reductase deficiency.
  18. 18. 5-alpha-reductase deficiency (5-ARD)  inability to convert testosterone to the more physiologically active dihydrotestosterone (DHT). Because DHT is required for the normal masculinization of the external genitalia in utero,  genetic males with 5-ARD are born with ambiguous genitalia (ie, male pseudohermaphroditism).  The described clinical abnormalities range from infertility with normal male genital anatomy to underdeveloped male with hypospadias to predominantly female external genitalia, most often with mild clitoromegaly.
  19. 19. Measuring the clitoris is an effective method for determining the degree of androgen effect. The clitoral index can be determined by measuring the glans of clitoris in the anteroposterior and transverse diameter. A clitoral index greater than 35 mm2 is evidence of increased androgen effect. A clitoral index greater than 100 mm2 is evidence of virilization. 5-alpha-reductase deficiency (5-ARD)
  20. 20. Imperforate hymen  Imperforate hymen represents the most common and most distal form of vaginal outflow obstruction.  Clinical presentations range from an incidental finding on physical examination of an asymptomatic patient to discovery on an evaluation for primary amenorrhea or abdominal or back pain.  The differential diagnosis of uterovaginal obstruction includes disorders of vaginal development, such as transverse vaginal septum or complete vaginal agenesis, Duplication anomalies of the uterovaginal tract often involve one tract that is decompressed and one that is obstructed.
  21. 21. Imperforate hymen
  22. 22. Etiology ofEtiology of secondary amenorrhoea
  23. 23. No features of androgen excess present • Physiological, e.g. pregnancy, lactation, menopause • Iatrogenic, e.g. depot medroxyprogesterone acetate contraceptive injection, radiotherapy, chemotherapy • Systemic disease, e.g. chronic illness, hypo- or hyperthyroidism • Uterine causes, e.g. cervical stenosis, Asherman's syndrome (intra- uterine adhesions) • Ovarian causes, e.g. premature ovarian failure, resistant ovary syndrome • Hypothalamic causes, e.g. weight loss, exercise, psychological distress, chronic illness, idiopathic • Pituitary causes, e.g. hyperprolactinaemia, hypopituitarism, Sheehan's syndrome • Causes of hypothalamic/pituitary damage, e.g. tumours, cranial irradiation, head injuries, sarcoidosis, tuberculosis
  24. 24. Features of androgen excess present • Polycystic ovary syndrome • Cushing's syndrome • Late-onset congenital adrenal hyperplasia • Adrenal or ovarian androgen-producing tumour
  25. 25. Polycystic ovary syndrome • This condition is characterized by hirsutism, acne, alopecia, infertility, obesity, and menstrual abnormalities (amenorrhoea in 19% of cases). • Ultrasound examination of the ovaries typically shows multiple, small peripheral cysts. up to a third of women in the general population have polycystic ovaries on ultrasound examination [DTB, 2001]. • Endocrine abnormalities include increased serum concentrations of testosterone, prolactin, luteinizing hormone (LH) (with normal follicle-stimulating hormone [FSH] levels), and insulin resistance with compensatory hyperinsulinaemia.
  26. 26. • Menopause/ovarian failure occurring before the age of 40 years is considered premature. • Auto-immune disease is the most common cause; auto-antibodies to ovarian cells, gonadotrophin receptors, and oocytes have been reported in 80% of cases. • Before puberty or in adolescents, ovarian failure is usually due to a chromosomal abnormality, e.g. Turner mosaic, or previous radiotherapy, or chemotherapy Premature ovarian failure
  27. 27. Ovarian failure (premature menopause( chromosomal anomalies autoimmune disease If the woman is under 30, a karyotype should be performed to rule out any mosaicism involving a Y chromosome. it is prudent to screen for thyroid, parathyroid, and adrenal dysfunction If a Y chromosome is found the gonads should be surgically excised. Laboratory evidence of autoimmune phenomenon is much more prevalent than clinically significant disease
  28. 28. autoimmune related dysfunction  The most common association is with thyroidThe most common association is with thyroid disease, but the parathyroids and adrenals can alsodisease, but the parathyroids and adrenals can also be affected.be affected.  Several studies have shown laboratory evidence ofSeveral studies have shown laboratory evidence of immune problems in about 15-40% of women withimmune problems in about 15-40% of women with premature ovarian failure.premature ovarian failure.  In general, ovarian biopsy is not indicated inIn general, ovarian biopsy is not indicated in patients with premature ovarian failure since nopatients with premature ovarian failure since no clinically useful information will be obtained.clinically useful information will be obtained.
  29. 29. Hyperprolactinaemia • A prolactinoma is the commonest cause of hyperprolactinaemia (60% of cases). • Other causes include non-functioning pituitary adenoma (disrupting the inhibitory influence of dopamine on prolactin secretion); • dopaminergic antagonist drugs (e.g. phenothiazines, haloperidol, clozapine, metoclopramide, domperidone, methyldopa, cimetidine); primary hypothyroidism (thyrotrophin-releasing hormone stimulates the secretion of prolactin), or it may be idiopathic. • Prolactin acts directly on the hypothalamus to reduce the amplitude and frequency of pulses of gonadotrophin- releasing hormone.
  30. 30. Weight-related amenorrhoea • A regular menstrual cycle is unlikely to occur if the body mass index (BMI) is less than 19 (normal range 20-25). • Weight loss may be due to illness, exercise, or eating disorders, among which anorexia nervosa lies at the extreme end of the spectrum.
  31. 31. Post-pill' amenorrhoea • This is defined as absence of menstruation for 6 months following cessation of the combined oral contraceptive pill. • It probably results from A transient inhibition of gonadotrophin-releasing hormone .
  32. 32. Progestogen-associated amenorrhoea • Depot medroxyprogesterone acetate inhibits the secretion of gonadotrophins and thus suppresses ovulation. • After 1 year of use, 80% of women have amenorrhoea or very scanty, infrequent vaginal bleeding. • There is partial oestrogen deficiency in women who use depot medroxyprogesterone acetate. • The progestogen-only pill leads to reversible long-term amenorrhoea in a minority of women, due to complete suppression of ovulation. • The levonorgestrel-releasing intra-uterine device commonly results in amenorrhoea after a few months. This is thought to be mainly a local effect, but suppression of ovulation can occur in some women (in some cycles).
  33. 33. ASSESSMENT of primaryASSESSMENT of primary amenorrheaamenorrhea
  34. 34. TSH elevated hypothyroidism Normal bone age delayed constitutional delay Normal LH, FSH, and prolactin levels elevated karyotype. low or within reference range head MRI 45,XO, the cause is gonadal dysgenesis 46,XX, the primary cause is ovarian failure •pituitary tumor or a brain lesion •drug use, an eating disorder, athleticism, or psychosocial stress. If puberty delayed
  35. 35. If the pregnancy test result is negative TSH and prolactin levels progestin challenge within reference range consider anovulatory cycles PCO E2/progestin challenge outlet obstruction obtain FSH and LH levels. low or within reference range head MRI. exclude chronic disease, anorexia nervosa, or psychosocial stress. high karyotype Turner synd. karyotype is normal (46,XX), the cause is ovarian failure elevated hypothyroidism and hyperprolactinemia +VE-VE If puberty not delayed +-
  36. 36. genital tract abnormalities karyotype If the karyotype is 46,XY If the karyotype is 46,XX testosterone levels male range female range androgen insensitivity. testicular regression or gonadal enzyme deficiency. müllerian agenesis (ie, Rokitansky-Kuster-Hauser syndrome).
  37. 37. Breast development, pubertal growth spurt, and adrenarche are delayed or absent in persons with hypothalamic pituitary failure.
  38. 38. adrenarche occurs normally, while estrogen-dependent breast development and the pubertal growth spurt are absent or delayed. isolated ovarian insufficiency or failure
  39. 39. Secondary AmenorrheaSecondary Amenorrhea
  40. 40. HistoryHistory A good history can reveal the etiologicA good history can reveal the etiologic diagnosis in up to 85% of cases ofdiagnosis in up to 85% of cases of amenorrhea.amenorrhea.
  41. 41. If the history and physicalIf the history and physical exam are suggestive of aexam are suggestive of a certain etiologycertain etiology ::  for the sake of efficiency and cost-for the sake of efficiency and cost- effectiveness, the workup caneffectiveness, the workup can sometimes be more directed accordingsometimes be more directed according to history.to history. ( in 85% of cases)
  42. 42. In patients that will not demonstrate anyIn patients that will not demonstrate any obvious etiology for their amenorrheaobvious etiology for their amenorrhea on history and physical exam. Theseon history and physical exam. These patients can be worked up in a logicalpatients can be worked up in a logical manner using a stepwise approach.manner using a stepwise approach.
  43. 43. How do I assess my patient with secondary amenorrhoea? • Risk of pregnancy • Associated symptoms, e.g. galactorrhoea, hirsutism, hot flushes, dry vagina, symptoms of thyroid disease • Recent change in body weight • Recent emotional upsets • Level of exercise • Previous menstrual and obstetric history • Previous surgery, e.g. endometrial curettage, oophorectomy • Previous abdominal, pelvic, or cranial radiotherapy • Family history, e.g. of early menopause • Drug history, e.g. progestogens, combined oral contraceptive, chemotherapy History
  44. 44. • Height and weight: calculate body mass index if appropriate. • Signs of excess androgens, e.g. hirsutism, acne • Signs of virilization, e.g. deep voice, clitoromegaly in addition to hirsutism, and acne • Signs of thyroid disease . • Acanthosis nigricans: this hyperpigmented thickening of the skin folds of the axilla and neck is a sign of profound insulin resistance. It is associated with polycystic ovary syndrome (PCOS) and obesity. • Breast examination for galactorrhoea. • Fundoscopy and assessment of visual fields if there is suspicion of pituitary tumour. • Pelvic examination . How do I assess my patient with secondary amenorrhoea? Examination
  45. 45. Preg.test TSH ,PROLACTIN’, Prog.challenge test withdrawal bleeding without withdrawal bleeding hypoestrogenic compromised outflow tract. + +ve.est,progest, challenge test -ve.est,progest challenge test FSH>30-40 Normal FSH HSG OR hysteroscopy asherman FSH low repeat Repeat+serum, est. level PROF hypothalamic- pituitary failure anovulation -VE
  46. 46. •Raised testosterone/androgen level. This group includes women with polycystic ovary syndrome (mildly raised level), and women with androgen-secreting tumours of the ovary or adrenal gland, late-onset congenital adrenal hyperplasia, or Cushing's syndrome. •Raised gonadotrophins (follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) with a low estradiol level. This group includes women with premature ovarian failure and resistant ovary syndrome. •Hyperprolactinaemia. This group includes women with prolactinomas and hypothyroidism. •Low gonadotrophins (FSH and LH) with a low estradiol level. This group includes women with amenorrhoea secondary to exercise, low weight, and stress. •Normal or mildly raised gonadotrophin levels with normal estradiol levels. This group includes women with polycystic ovary syndrome (PCOS) or other mild disorders of gonadotrophin regulation or action.
  47. 47. Complications and prognosis • Osteoporosis: women with amenorrhoea associated with oestrogen deficiency are at significant risk of developing osteoporosis. This increased risk persists even if normal menses are resumed. Oestrogen deficiency is of particular concern in younger women as a desirable peak bone mass may not be attained • Cardiovascular disease • Young women with amenorrhoea associated with oestrogen deficiency may be at increased risk of cardiovascular disease • Women with polycystic ovary syndrome have an increased risk of developing cardiovascular disease, hypertension, and type 2 diabetes [Hopkinson et al, 1998].
  48. 48. • Endometrial hyperplasia: women with amenorrhoea but no associated oestrogen deficiency are at increased risk of endometrial hyperplasia and endometrial carcinoma . • Infertility: women with amenorrhoea generally do not ovulate. • Psychological distress: amenorrhoea often causes considerable anxiety, Many women have concerns about loss of fertility, loss of femininity, or worry about an unwanted pregnancy. The diagnosis of Turner's syndrome, testicular feminization, or developmental anomaly can be traumatic for both girls and their parents . Complications and prognosis
  49. 49. Thank youThank you

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