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Year 2 Medicine > Disorders of Ovulation > Flashcards

Disorders of Ovulation Flashcards

1
Q

Menstrual cycle

  • Whenever you measure any of the hormones (E.g. oestrogen, progesterone, LH, FSH) you must note where within a women’s cycle you are taking the blood test.
    • Preovulatory surge in … and …
    • … rises and falls just before the Preovulatory surge and then have a secondary rise in the … phase of the cycle
    • Progesterone levels low in … phase of the cycle - then provided the cycle has been ovulatory and … … formed - progesterone levels peak as they are produced by this
    • Alongside the menstrual cycle there is an … cycle - with a … phase followed by the … phase
A
  • Whenever you measure any of the hormones (E.g. oestrogen, progesterone, LH, FSH) you must note where within a women’s cycle you are taking the blood test.
    • Preovulatory surge in LH and FSH
    • Estradiol rises and falls just before the Preovulatory surge and then have a secondary rise in the luteal phase of the cycle
    • Progesterone levels low in follicular phase of the cycle - then provided the cycle has been ovulatory and corpus luteum formed - progesterone levels peak as they are produced by this
    • Alongside the menstrual cycle there is an endometrial cycle - with a proliferative phase followed by the secretory phase
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2
Q

Central mediator: Kisspeptin

  • A GnRH …: at the … of the reproductive axis in the …
  • KISS1 neurons highly responsive to …, implicated in both + and – central feedback of sex steroids on … production
  • … influences on reproduction
    • mediated by … via the kisspeptin system
    • … effect on puberty & reproduction
A
  • A GnRH secretagogue: at the apex of the reproductive axis in the hypothalamus
  • KISS1 neurons highly responsive to oestrogen, implicated in both + and – central feedback of sex steroids on GnRH production
  • Metabolic influences on reproduction
    • mediated by leptin via the kisspeptin system
    • permissive effect on puberty & reproduction
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3
Q

Diagnosis of ovulation - Clinical

  • Take a … from the women
  • Regular menstruation usually … days (check not on … …)
  • Mid cycle … at ovulation
  • vaginal discharge alters (… muscus post ovulation)
A
  • Take a history from the women
  • Regular menstruation usually 28 days (check not on hormonal contraceptives)
  • Mid cycle pain at ovulation
  • vaginal discharge alters (increased muscus post ovulation)
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4
Q

Diagnosis of ovulation - Biochemistry / Tests

  • Day 21 … blood test (7 days before start of next menstrual period)
  • … detection kits: urinary kits bought over the counter
  • … … ultrasound done from Day …, alternate days to demonstrate the developing follicle size and Corpus …
    • NOT - … body temperature, cervical … change, vaginal … changes nor … biopsies
A
  • Day 21 progesterone blood test (7 days before start of next menstrual period)
  • LH detection kits: urinary kits bought over the counter
  • Tranvaginal pelvis ultrasound done from Day 10, alternate days to demonstrate the developing follicle size and Corpus Luteum
    • NOT - basal body temperature, cervical mucus change, vaginal epithelium changes nore endometrial biopsies
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5
Q

Define Amenorrhoea

A

Lack of a period for more than 6 months

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6
Q

Define Primary Amenorrhoea

A

Never had a period (never went through menarche)

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7
Q

Define Secondary Amenorrhoea

A

Has menstruated before (lack of period for >6months)

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8
Q

Define Oligomenorrhoea

A

Irregular periods - usually occuring more than 6 weeks apart

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9
Q

Define Polymenorrhoea

A

Periods occuring less than 3 weeks apart

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10
Q

Causes of Ovulation Problems:

  • … (lack of GnRH)
    • GnRH deficiency (… syndrome)
      • may be associated with …
    • ‘…’ hypothalamic amenorrhoea
      • weight …/… related/excessive …
      • People with … disorders e.g.
  • Pituitary (lack of … and …)
    • pituitary tumours (…/other tumours)
    • post pituitary … /…
A
  • Hypothalamus (lack of GnRH)
    • GnRH deficiency (Kallmann’s syndrome)
      • may be associated with anosmia
    • ‘Functional’ hypothalamic amenorrhoea
      • weight loss/stress related/excessive exercise
      • anorexia nervosa/bulimia
  • Pituitary (lack of FSH and LH)
    • pituitary tumours (prolactinoma/other tumours)
    • post pituitary surgery /radiotherapy
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11
Q

Causes of Ovulation Problems

  • Ovary
    • Premature ovarian …
      • Chromosomal abnormalities eg … syndrome
      • Autoimmune
      • Iatrogenic
        • Patients who have had …/…./…
  • Hyperandrogenism
    • … … syndrome : commonest cause
      • … adrenal …
A
  • Ovary
    • Premature ovarian insufficiency
      • Chromosomal abnormalities eg Turner syndrome
      • Autoimmune
      • Iatrogenic
        • Surgery/chemotherapy/radiotherapy
  • Hyperandrogenism
    • Polycystic ovarian syndrome: commonest cause
    • Congenital adrenal hyperplasia
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12
Q

Hirsutism

  • ‘…-dependent’ hirsutism
    • Excess … … in a male distribution
  • NOT:
    • –…-… hair growth
      • known as Hyper…
  • … / … hair growth
A
  • ‘Androgen-dependent’ hirsutism
    • Excess body hair in a male distribution
  • NOT:
    • Androgen-independent hair growth
      • Hypertrichosis
  • Familial / racial hair growth
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13
Q

Differentiatial Diagnosis of Hirsutism

  • 95% due to … or ‘… hirsutism’
  • 1% Non-classical … … …(CAH)
  • <1% … syndrome
  • <1% Adrenal / ovarian …
    *
A
  • 95% PCOS or ‘idiopathic hirsutism’
  • 1% Non-classical congenital adrenal hyperplasia (CAH)
  • <1% Cushing’s syndrome
  • <1% Adrenal / ovarian tumour
  • Prevalence of polycystic ovarian syndrome:
  • 5-10% women!
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14
Q

Prevalence of polycystic ovarian syndrome: …-…% of women

A

5-10% women!

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15
Q

When to worry about Hirsutism

  • … onset of … symptoms
  • V…
    • Frontal …
    • … of voice
    • …-type … mass
    • Clitoro…
  • Possible … syndrome
A
  • Sudden onset of severe symptoms
  • Virilisation
    • Frontal balding
    • Deepening of voice
    • Male-type muscle mass
    • Clitoromegaly
  • Possible Cushing’s syndrome
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16
Q

Clinical Features of PCOS

  • Hyper…
    • Causing H… and a…
  • Chronic … / …
    • < (and including) … periods / year
    • S…
  • … (but …% of women with PCOS are “lean”)
A
  • Hyperandrogenism
    • Hirsutism, acne
  • Chronic oligomenorrhoea / amenorrhoea
    • < (and including) 9 periods / year
    • Subfertility
  • Obesity (but 25% of women with PCOS are “lean”)
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17
Q

USS Appearance of Polycystic Ovaries

  • > and including 10 … follicules …-…mm in diameter, arranged around a thickened ovarian stroma
    • Do all women with PCOS have USS appearance?
A
  • > and including 10 subcapsular follicules 2-6mm in diameter, arranged around a thickened ovarian stroma
  • not all women with PCOS will have USS appearance
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18
Q

What is this USS showing?

A

PCOS

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19
Q

Hormonal Abnormalities in PCOS

  • Raised baseline … and normal … levels. Ratio is …:1
  • Raised … and free …
  • Reduced … (SHBG)
  • … usually normal
A
  • Raised baseline LH and normal FSH levels. Ratio LH:FSH 3:1
  • Raised androgens and free testosterone
  • Reduced Sex Hormone Binding Globin (SHBG)
  • Oestrogen usually normal
20
Q

Sex hormone Binding Globulin

  • Produced by the …
  • Binds … and …
  • If … bound - not converted to … component dihydrotestosterone ie not “…”
  • SHBG increased by …
  • SHBG decreased by … thus releasing more free …
A
  • Produced by the liver
  • Binds testosterone and oestradiol
  • If testosterone bound - not converted to active component dihydrotestosterone ie not “free”
  • SHBG increased by oestrogens
  • SHBG decreased by testosterone thus releasing more free testosterone
21
Q

PCOS and the Metabolic Syndrome

  • … resistance with increased …
    • increased … production by ovarian … cells
    • decreased … production by the liver
  • Impaired … tolerance
    • increased risk … DM and T2 DM
  • Dys…
  • … dysfunction
  • ? ­ risk cardiovascular disease ?
A
  • Insulin resistance with insulin
    • increased androgen production by ovarian theca cells
    • decreased SHBG production by the liver
  • Impaired glucose tolerance
    • risk gestational DM and T2 DM
  • Dyslipidaemia
  • Vascular dysfunction
  • ? ­ risk cardiovascular disease ?
22
Q

Potential consequences of … resistance in women with PCOS

A

Potential consequences of insulin resistance in women with PCOS

23
Q

Reproductive Effects of PCOS

  • PCOS is maybe associated with varying degrees of …
    • …% of all causes of infertility is lack of ovulation
      • …% of lack of ovulation due to PCOS
  • Associated with increased …
  • Increased risk of … Diabetes
A
  • PCOS is maybe associated with varying degrees of infertility
    • 15% of all causes of infertility is lack of ovulation
      • 80% of lack of ovulation due to PCOS
  • Associated with increased miscarriages
  • Increased risk of Gestational Diabetes
24
Q

PCOS and Endometrial Cancer

  • Increased endometrial … and …
  • Lack of … on the endometrium
  • Endometrial cancer associated with … & …
A
  • Increased endometrial hyperplasia and cancer
  • Lack of progesterone on the endometrium
  • Endometrial cancer associated with type 2 diabetes & obesity
25
Q

Treatment of PCOS - Lifestyle modifications

  • Diet & exercise
  • Stop …
  • RESULTS:
    • … insulin resistance
    • … [SHBG]
    • … [free testo]
    • Improved fertility / pregnancy outcomes
    • Improve … syndrome risk factors
  • High frequency … disorders
    • … associated with PCOS
  • Lean women with PCOS should …
A
  • Diet & exercise
  • Stop smoking
  • RESULTS:
    • decreased insulin resistance
    • increased [SHBG]
    • decreased [free testo]
    • Improved fertility / pregnancy outcomes
    • Improve metabolic syndrome risk factors
  • High frequency eating disorders
    • Bulimia associated with PCOS
  • Lean women with PCOS should try not to get fat!
26
Q

Treatment of PCOS - Combined Oral Contraceptives

  • Increases … and thus … free testosterone
  • Decreases … & … and therefore ovarian stimulation
  • … cycle & decreases endometrial …
  • BUT may cause weight …, venous …, adverse effects on … risk factors
A
  • Increases SHBG and thus decreases free testosterone
  • Decreases FSH & LH and therefore ovarian stimulation
  • Regulates cycle & decreases endometrial hyperplasia
  • BUT may cause weight gain, venous thrombosis, adverse effects on metabolic risk factors
27
Q

Anti-androgens

  • With … / other form of …
  • Cyproterone A… (oral tablet)
    • inhibits binding of testosterone & 5 alpha dihydrotestosterone to androgen receptors
  • S… (oral tablet)
    • anti mineralocorticoid and anti androgen properties
A
  • With COCP / other form of secure contraception
  • Cyproterone Acetate (oral tablet)
    • inhibits binding of testosterone & 5 alpha dihydrotestosterone to androgen receptors
  • Spironolactone (oral tablet)
    • anti mineralocorticoid and anti androgen properties
28
Q

Targeting Insulin Resistance in PCOS

  • Metformin (biguanide)
    • Decreased insulin resistance, decreased insulin levels, decreased ovarian … production
  • May help with … loss / … prevention
  • May increase­ … (with clomifene), safe in …
  • Less helpful for … & …, but may be an option for … PCOS women
A
  • Metformin (biguanide)
    • Decreased insulin resistance, decreased insulin levels, decreased ovarian androgen production
  • May help with weight loss / diabetes prevention
  • May increase­ ovulation (with clomifene), safe in pregnancy
  • Less helpful for hirsutism & oligomenorrhoea, but may be an option for obese PCOS women
29
Q

Hair removal - women with Hirsutism

  • … (laser) / electrolysis etc
  • … cream (non-NHS)
    • Inhibits ornithine decarboxylase enzyme in hair follicles
A
  • Photoepilation (laser) / electrolysis etc
  • Eflornithine cream (non-NHS)
    • Inhibits ornithine decarboxylase enzyme in hair follicles
30
Q

… is an option for fertility/ovulation in people with PCOS

A

Clomifene is an option for fertility/ovulation in people with PCOS

31
Q

Primary Ovarian Insufficiency

  • Presentation:
    • Primary or secondary …
      • Secondary … may be associated with hot flushes & sweats
  • Other terms used:
    • Premature ovarian …
    • Premature …
  • Aetiology:
    • Autoimmunity
      • May be associated with other autoimmune endocrine conditions
    • X chromosomal abnormalities
      • … syndrome
      • … … associated
  • Genetic predisposition
    • Premature menopause
  • Iatrogenic
    • Surgery, radiotherapy or chemotherapy
A
  • Presentation:
    • Primary or secondary amenorrhoea
      • Secondary amenorrhoea may be associated with hot flushes & sweats
  • Other terms used:
    • Premature ovarian failure
    • Premature menopause
  • Aetiology:
    • Autoimmunity
      • May be associated with other autoimmune endocrine conditions
    • X chromosomal abnormalities
      • Turner syndrome
      • Fragile X associated
  • Genetic predisposition
    • Premature menopause
  • Iatrogenic
    • Surgery, radiotherapy or chemotherapy
32
Q

Premature Ovarian Failure: Investigations

  • history / examination
  • High … and …
  • ? K…
  • Consider pelvic …
  • Consider screening for other … endocrine disease
    • … function tests, …, …
A
  • history / examination
  • High LH and FSH
  • ? Karyotype
  • Consider pelvic USS
  • Consider screening for other autoimmune endocrine disease
    • Thyroid function tests, glucose, cortisol
33
Q

Premature Ovarian Failure: Management

  • Management:
    • … support
    • HRT
      • Continue till ± age …
  • Monitor bone …
    • … scan
  • Fertility
    • … with donor egg
A
  • Management:
    • Psychological support
    • HRT - hormone replacement therapy
      • Continue till ± 52
  • Monitor bone density
    • DEXA scan
  • Fertility
    • IVF with donor egg
34
Q

Turner Syndrome

  • Complete / partial … … in some / all cells
    • …% of cases will be …
    • Rest: partial absence of X or mosaicism
  • How common? 1 in …
    • What gender?
  • Presentation
    • May be diagnosed in the …
    • May present with … stature in childhood
    • May present with … / … …
A
  • Complete / partial X monosomy in some / all cells
    • 50% of cases will be XO
    • Rest: partial absence of X or mosaicism
  • 1:2000 – 1:2500 live-born girls
  • Presentation
    • May be diagnosed in the neonate
    • May present with short stature in childhood
    • May present with primary / secondary amenorrhoea
35
Q

Turner Syndrome - Associated Problems

  • … stature
    • Consider … treatment
  • CV system
    • … of aorta
    • … aortic valve
    • Aortic …
    • … (Adults)
  • Renal
    • … abnormalities
  • … syndrome
  • …thyroidism
  • Ears/… problems
  • … (lack HRT)
A
  • Short stature
    • Consider GH treatment
  • CV system
    • Coarctation of aorta
    • Bicuspid aortic valve
    • Aortic dissection
    • Hypertension (Adults)
  • Renal
    • Congenital abnormalities
  • Metabolic syndrome
  • Hypothyroidism
  • Ears/hearing problems
  • Osteoporosis (lack HRT)
36
Q

Congenital Adrenal Hyperplasia

  • disorders of … biosynthesis
    • Carrier frequency 1 : …
    • Most patients are compound …
      • Different mutations on … alleles
  • …% CAH cases caused by 21-hydroxylase deficiency
    • … deficiency
    • May have … deficiency
    • … excess
    • Depends on degree of enzyme …
A
  • disorders of cortisol biosynthesis
    • Carrier frequency 1 : 60
    • Most patients are compound heterozygotes
      • Different mutations on two alleles
  • 95% CAH cases caused by 21-hydroxylase deficiency
    • Cortisol deficiency
    • May have aldosterone deficiency
    • Androgen excess
    • Depends on degree of enzyme deficiency
37
Q

Congenital Adrenal Hyperplasia - Diagnosis

  • High concentrations of 17-…
  • Can confirm with … test
A
  • High concentrations of 17-hydroxyprogesterone
  • Can confirm with Synacthen test
38
Q

CAH Presentation

  • CHILDHOOD
    • ‘Classic’ / ‘severe’
    • …-losing (2/3rd)
    • Non-… losing (1/3rd)
    • Simple vi…
  • ADULTHOOD
    • ‘Non-classic’ / ‘…’
    • ‘…-onset’
A
  • CHILDHOOD
    • ‘Classic’ / ‘severe’
    • Salt-losing (2/3rd)
    • Non-Salt losing (1/3rd)
    • Simple virilising
  • ADULTHOOD
    • ‘Non-classic’ / ‘mild’
    • ‘late-onset’
39
Q

CAH Presentation - Childhood

  • … wasting
    • H…, S…
  • V…
    • Ambiguous genitalia in …
    • Early … in boys
  • … puberty
  • Abnormal …
    • … early
    • … fusion
A
  • Childhood:
    • Salt wasting
      • Hypovolaemia, shock
    • Virilisation
      • Ambiguous genitalia in girls
      • Early virilisation in boys
    • Precocious puberty
    • Abnormal growth
      • Accelerated early
      • Premature fusion
40
Q

CAH Presentation - Adulthood (mild)

  • Adulthood (mild):
    • H…
    • O.. / a…
    • A…
    • S…
    • Similar to ‘…’ presentation
A
  • Adulthood (mild):
    • Hirsutism
    • Oligo / amenorrhoea
    • Acne
    • Subfertility
    • Similar to ‘PCOS’ presentation
41
Q

CAH Treatment

  • … & …. replacement
    • Such as H… & F…
    • Additional … in infancy
  • … treament will suppress CRH / ACTH
  • Supraphysiological … doses may be needed to suppress adrenal … production
    • Monitor [17-OH-P] / androstenedione
    • Monitor … in childhood
      • Excess … treatment may … growth
  • … management for ambiguous genitalia
  • Non-classical CAH in adult women (mild)
    • Can treat as for … with COCP ± anti-androgen
A
  • Glucorticoid & mineralocorticoid replacement
    • Hydrocortisone & fludrocortisone
    • Additional salt in infancy
  • Glucocorticoids suppress CRH / ACTH
  • Supraphysiological glucocorticoid doses may be needed to suppress adrenal androgen production
    • Monitor [17-OH-P] / androstenedione
    • Monitor growth in childhood
      • Excess glucocorticoid treatment may inhibit growth
  • Surgical management for ambiguous genitalia
  • Non-classical CAH in adult women (mild)
    • Can treat as for PCOS with COCP ± anti-androgen
42
Q

Why have her Periods stopped?

  1. Beth – 23, BMI 17 kg/m2, triathlete
  2. Carol – 33, risperidone treatment, galactorrhoea
  3. Amy – 17, short stature, aortic regurgitation
  4. Marjorie – 50, hot flushes and sweats
  5. Emma – 28, breast tenderness, nausea
A
  1. Beth – 23, BMI 17 kg/m2, triathlete
    • Hypothalamic amenorrhoea
  2. Carol – 33, risperidone treatment, galactorrhoea
    • Hyperprolactinaemia due to medication
  3. Amy – 17, short stature, aortic regurgitation
    • Turner syndrome
  4. Marjorie – 50, hot flushes and sweats
    • Menopause
  5. Emma – 28, breast tenderness, nausea
    • Pregnancy
43
Q

Treatment options for PCOS​

No prescription required:​ (3) vs On prescription: (4)

A
  1. Diet / exercise
  2. Smoking cessation
  3. Epilation
  • Prescription:
  1. Combined oral contraceptive pill
    1. –+/- anti-androgens
  2. Metformin
  3. (Eflornithine cream)
  4. Clomifene - To induce ovulation
44
Q

Clinical features of PCOS​

Woman presents with: (4) v Medical terminology: (4)

A
  1. Unwanted hair growth in a male distribution = Hirsutism
  2. Spots = Acne
  3. Irregular menstrual periods = Oligomenorrhoea
  4. Trying to conceive without success = Subfertility
45
Q

To confirm ovulation…

  • History
  • Over the counter test
  • Blood test
  • Imaging test in subfertility clinic
A

History

  • 28 day menstrual cycle

Over the counter test

  • LH detection in urine

Blood test

  • 21 day progesterone

Imaging test in subfertility clinic

  • Trans-vaginal USS (follicle tracking)
46
Q

Definitions - Disorders of Ovulation

  • A girl who does not go through menarche
    • …
  • A woman whose periods stop aged 26
    • …
  • A woman having 8 menstrual periods per year
    • …
  • A woman having menstrual periods every 3 weeks
    • …
A
  • A girl who does not go through menarche
    • Primary amenorrhoea
  • A woman whose periods stop aged 26
    • Secondary amenorrhoea
  • A woman having 8 menstrual periods per year
    • Oligomenorrhoea
  • A woman having menstrual periods every 3 weeks
    • Polymenorrhoea

Year 2 Medicine (162 decks)

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