Disorders of Ovulation Flashcards
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
- 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

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 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

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)
- 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)

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
- 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
Define Amenorrhoea
Lack of a period for more than 6 months
Define Primary Amenorrhoea
Never had a period (never went through menarche)
Define Secondary Amenorrhoea
Has menstruated before (lack of period for >6months)
Define Oligomenorrhoea
Irregular periods - usually occuring more than 6 weeks apart
Define Polymenorrhoea
Periods occuring less than 3 weeks apart
Causes of Ovulation Problems:
- … (lack of GnRH)
- GnRH deficiency (… syndrome)
- may be associated with …
- ‘…’ hypothalamic amenorrhoea
- weight …/… related/excessive …
- People with … disorders e.g.
- GnRH deficiency (… syndrome)
- Pituitary (lack of … and …)
- pituitary tumours (…/other tumours)
- post pituitary … /…
-
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
- GnRH deficiency (Kallmann’s syndrome)
- Pituitary (lack of FSH and LH)
- pituitary tumours (prolactinoma/other tumours)
- post pituitary surgery /radiotherapy
Causes of Ovulation Problems
- Ovary
- Premature ovarian …
- Chromosomal abnormalities eg … syndrome
- Autoimmune
- Iatrogenic
- Patients who have had …/…./…
- Premature ovarian …
- Hyperandrogenism
- … … syndrome : commonest cause
- … adrenal …
- … … syndrome : commonest cause
- Ovary
- Premature ovarian insufficiency
- Chromosomal abnormalities eg Turner syndrome
- Autoimmune
- Iatrogenic
- Surgery/chemotherapy/radiotherapy
- Premature ovarian insufficiency
- Hyperandrogenism
- Polycystic ovarian syndrome: commonest cause
- Congenital adrenal hyperplasia
Hirsutism
- ‘…-dependent’ hirsutism
- Excess … … in a male distribution
- NOT:
- –…-… hair growth
- known as Hyper…
- –…-… hair growth
- … / … hair growth
- ‘Androgen-dependent’ hirsutism
- Excess body hair in a male distribution
- NOT:
-
Androgen-independent hair growth
- Hypertrichosis
-
Androgen-independent hair growth
- Familial / racial hair growth
Differentiatial Diagnosis of Hirsutism
- 95% due to … or ‘… hirsutism’
- 1% Non-classical … … …(CAH)
- <1% … syndrome
- <1% Adrenal / ovarian …
*
- 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!
Prevalence of polycystic ovarian syndrome: …-…% of women
5-10% women!
When to worry about Hirsutism
- … onset of … symptoms
- V…
- Frontal …
- … of voice
- …-type … mass
- Clitoro…
- Possible … syndrome
- Sudden onset of severe symptoms
-
Virilisation
- Frontal balding
- Deepening of voice
- Male-type muscle mass
- Clitoromegaly
- Possible Cushing’s syndrome
Clinical Features of PCOS
- Hyper…
- Causing H… and a…
- Chronic … / …
- < (and including) … periods / year
- S…
- … (but …% of women with PCOS are “lean”)
- Hyperandrogenism
- Hirsutism, acne
- Chronic oligomenorrhoea / amenorrhoea
- < (and including) 9 periods / year
- Subfertility
- Obesity (but 25% of women with PCOS are “lean”)

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?

- > and including 10 subcapsular follicules 2-6mm in diameter, arranged around a thickened ovarian stroma
- not all women with PCOS will have USS appearance
What is this USS showing?

PCOS
Hormonal Abnormalities in PCOS
- Raised baseline … and normal … levels. Ratio is …:1
- Raised … and free …
- Reduced … (SHBG)
- … usually normal
- 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
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 …
- 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

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 ?
-
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 ?
Potential consequences of … resistance in women with PCOS

Potential consequences of insulin resistance in women with PCOS
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
- …% of all causes of infertility is lack of ovulation
- Associated with increased …
- Increased risk of … Diabetes
- 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
-
15% of all causes of infertility is lack of ovulation
- Associated with increased miscarriages
- Increased risk of Gestational Diabetes
PCOS and Endometrial Cancer
- Increased endometrial … and …
- Lack of … on the endometrium
- Endometrial cancer associated with … & …
- Increased endometrial hyperplasia and cancer
- Lack of progesterone on the endometrium
- Endometrial cancer associated with type 2 diabetes & obesity
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 …
- 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!
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
- 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
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
- 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
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
- 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
Hair removal - women with Hirsutism
- … (laser) / electrolysis etc
- … cream (non-NHS)
- Inhibits ornithine decarboxylase enzyme in hair follicles
- Photoepilation (laser) / electrolysis etc
-
Eflornithine cream (non-NHS)
- Inhibits ornithine decarboxylase enzyme in hair follicles
… is an option for fertility/ovulation in people with PCOS
Clomifene is an option for fertility/ovulation in people with PCOS
Primary Ovarian Insufficiency
-
Presentation:
- Primary or secondary …
- Secondary … may be associated with hot flushes & sweats
- Primary or secondary …
-
Other terms used:
- Premature ovarian …
- Premature …
-
Aetiology:
- Autoimmunity
- May be associated with other autoimmune endocrine conditions
- X chromosomal abnormalities
- … syndrome
- … … associated
- Autoimmunity
- Genetic predisposition
- Premature menopause
- Iatrogenic
- Surgery, radiotherapy or chemotherapy
-
Presentation:
- Primary or secondary amenorrhoea
- Secondary amenorrhoea may be associated with hot flushes & sweats
- Primary or secondary amenorrhoea
-
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
- Autoimmunity
- Genetic predisposition
- Premature menopause
- Iatrogenic
- Surgery, radiotherapy or chemotherapy
Premature Ovarian Failure: Investigations
- history / examination
- High … and …
- ? K…
- Consider pelvic …
- Consider screening for other … endocrine disease
- … function tests, …, …
- history / examination
- High LH and FSH
- ? Karyotype
- Consider pelvic USS
- Consider screening for other autoimmune endocrine disease
- Thyroid function tests, glucose, cortisol
Premature Ovarian Failure: Management
- Management:
- … support
- HRT
- Continue till ± age …
- Monitor bone …
- … scan
- Fertility
- … with donor egg
- Management:
- Psychological support
- HRT - hormone replacement therapy
- Continue till ± 52
- Monitor bone density
- DEXA scan
- Fertility
- IVF with donor egg
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 … / … …
- 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
Turner Syndrome - Associated Problems
- … stature
- Consider … treatment
- CV system
- … of aorta
- … aortic valve
- Aortic …
- … (Adults)
- Renal
- … abnormalities
- … syndrome
- …thyroidism
- Ears/… problems
- … (lack HRT)
-
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)

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 …
- 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

Congenital Adrenal Hyperplasia - Diagnosis
- High concentrations of 17-…
- Can confirm with … test
- High concentrations of 17-hydroxyprogesterone
- Can confirm with Synacthen test
CAH Presentation
- CHILDHOOD
- ‘Classic’ / ‘severe’
- …-losing (2/3rd)
- Non-… losing (1/3rd)
- Simple vi…
- ADULTHOOD
- ‘Non-classic’ / ‘…’
- ‘…-onset’
-
CHILDHOOD
- ‘Classic’ / ‘severe’
- Salt-losing (2/3rd)
- Non-Salt losing (1/3rd)
- Simple virilising
-
ADULTHOOD
- ‘Non-classic’ / ‘mild’
- ‘late-onset’
CAH Presentation - Childhood
- … wasting
- H…, S…
- V…
- Ambiguous genitalia in …
- Early … in boys
- … puberty
- Abnormal …
- … early
- … fusion
- Childhood:
-
Salt wasting
- Hypovolaemia, shock
-
Virilisation
- Ambiguous genitalia in girls
- Early virilisation in boys
- Precocious puberty
-
Abnormal growth
- Accelerated early
- Premature fusion
-
Salt wasting
CAH Presentation - Adulthood (mild)
- Adulthood (mild):
- H…
- O.. / a…
- A…
- S…
- Similar to ‘…’ presentation
- Adulthood (mild):
- Hirsutism
- Oligo / amenorrhoea
- Acne
- Subfertility
- Similar to ‘PCOS’ presentation
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
-
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
Why have her Periods stopped?
- Beth – 23, BMI 17 kg/m2, triathlete
- Carol – 33, risperidone treatment, galactorrhoea
- Amy – 17, short stature, aortic regurgitation
- Marjorie – 50, hot flushes and sweats
- Emma – 28, breast tenderness, nausea
- Beth – 23, BMI 17 kg/m2, triathlete
- Hypothalamic amenorrhoea
- Carol – 33, risperidone treatment, galactorrhoea
- Hyperprolactinaemia due to medication
- Amy – 17, short stature, aortic regurgitation
- Turner syndrome
- Marjorie – 50, hot flushes and sweats
- Menopause
- Emma – 28, breast tenderness, nausea
- Pregnancy
Treatment options for PCOS
No prescription required: (3) vs On prescription: (4)
- Diet / exercise
- Smoking cessation
- Epilation
- Prescription:
- Combined oral contraceptive pill
- –+/- anti-androgens
- Metformin
- (Eflornithine cream)
- Clomifene - To induce ovulation
Clinical features of PCOS
Woman presents with: (4) v Medical terminology: (4)
- Unwanted hair growth in a male distribution = Hirsutism
- Spots = Acne
- Irregular menstrual periods = Oligomenorrhoea
- Trying to conceive without success = Subfertility
To confirm ovulation…
- History
- Over the counter test
- Blood test
- Imaging test in subfertility clinic
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)
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 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