reproductive hormone test requesting jeffrey barron consultant chemical pathologist epsom & st...
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REPRODUCTIVE HORMONE
TEST REQUESTING
Jeffrey BarronConsultant Chemical PathologistEpsom & St Helier University Hospitals
03.07.2007
EFFECTIVE REPRODUCTIVE HORMONE TEST REQUESTING EASY GUIDE
Jeffrey BarronChemical PathologistLabtests
Goodfellows 24.03.2112
Outline of Talk - Female• Laboratory role• Hypothalamic-Pituitary-Ovarian axis• Amenorrhoea: Secondary
– Oligo- & Amenorrhoea:• FSH interpretation• Prolactin Raised: Galactorrhoea • Testosterone raised:
–Polycystic Ovarian Syndrome –Hirsutism, Virilisation
• Menopause• Infertility - Subfertility • Recommendations for requesting
Laboratory Role: As You May See It
Specimen
Input Process
Lab
Output
Results
Productivity
Request
Laboratory Role: How We Add Value
Input
Clinical &ScientificExpertise
Process Output
ReasonRequest
Tests
Data Knowledge,Expert
Algorithms
ClinicalAdvice
Lab
Productivity
Value
Value Value
Hypothalamic-Pituitary-Ovarian axis
uterus
menses
Testosterone-theca cells/stroma
Amenorrhoea ?
Amenorrhoea
• Physiological– Prior to puberty – Pregnancy– Lactation– Menopause• Secondary– Gynaecological disorder – Systemic disease
FSH & LH levels vary
FSH levels vary
Amenorrhoea ?
Amenorrhoea ?
• Consider: - Pregnancy- Lactation
- Exercise- Weight loss / Coeliac disease- Severe illness
• If none of above request: - FSH, LH - Prolactin- Testosterone- Oestradiol to interpret FSH or guide Rx - Consider TSH
Oligo- & Amenorrhoea: SecondaryPreviously regular-None for 6 months
Amenorrhoea ?
• FSH high:Ovarian failure – early karyotype• FSH low to low normal:
- Pregnancy- Lactation
- Exercise- Weight loss- Severe illness- Stress- Contraceptive drugs- Hypothalamic/Pituitary disease
or masses•Uterine: Asherman’s syndrome
Oligo- & Amenorrhoea: Secondary
FSH
• Pregnancy• Lactation• Stress• Drugs: neuroleptics, SSRI, tricyclics, metoclopramide, domperidone, other• 1o hypothyroidism• Macroprolactin - prolactin~IgG• Pituitary adenoma
Oligo- & Amenorrhoea: Secondary
Prolactin raised
Galactorrhoea - 1
Juno holding her breast for Hercules in The birth of the Milky Way, Peter Paul Rubens1637
• Sample Collection: day 2 - 5, after midday: menses + diurnal rhythms
• Galactorrhoea &/or oligo-amenorrhoea + raised prolactin + correct sample + no medication + not macroprolactin+ not pregnant, lactation, hypothyroidism = possible prolactinoma
GalactorrhoeaProlactin raised
• Prolactin 500 - 800 mIU/L
- Suggest review medication
- Examine for galactorrhoea
- Repeat on day 2 – 5, after midday
• Repeat or > 800 mIU/L- Lab phone to review medication,
lactation, clinical- Exclude macroprolactin: prolactin~IgG
- Recommend: Repeat on day 2 – 5 Endocrine referral
Raised ProlactinNo Galactorrhoea or Amenorrhoea
Hirsutism
• PCOS - most common cause
• Hirsutism:mildsevere
• Virilisation
Oligo- & Amenorrhoea: SecondaryTestosterone raised
Ferriman-Gallwey hirsutism scoring system
Testosterone Total vs Hirsutism Score
Mayo Clinic specific testosterone assay
RS Legro et al, Total Testosterone Assays in Women with Polycystic Ovary Syndrome: Precision and Correlation with Hirsutism, J Clin Endocrinol Metab. 2010; 95: 5305–5313
Hirsutism Score
2.6 nmol/L
4.5
Testosterone
Ideal diagnostic test
Normal Disease
No false positives or negatives
Probability
No disease
Normal
Reference interval 95%
PCOS or Hirsutism
No
. of i
nd
ivid
ua
ls
Concentration
Testosterone in PCOS
False positivesFalse negatives
Hirsutism
Polycystic Ovarian Syndrome - 1
• Common, 5 – 10% young women• 21% NZ women, reproductive age
– ultrasound shows PCO• Presentation: ~ half patients
– Anovulatory infertility– Oligomenorrhoea– Hirsutism, acne, male type baldness
• Familial• Linked: type II diabetes
Hypothalamic-Pituitary-Ovarian axis
uterus
menses
Testosterone-theca cells/stroma
Hirsutism & Acne
Polycystic Ovarian Syndrome – 2
Diagnosis• Request: Testosterone, day 2 - 5
– Increased ~ 70% patients PCOS– Fulfills 1 of 3 criteria for diagnosis
• Other criteria:– Oligo- &/or anovulation– Ultrasound PCO
• FSH & LH NOT reliable criteria• Clinically Testosterone not necessary
Martin KA et al DIAGNOSIS AND EVALUATION OF WOMEN WITH PREMENOPAUSAL HIRSUTISM J Clin Endocrinol Metab: 93 (4), 1105-1120, 2008
Fritz M & Speroff L, Clinical Gynaecological Endocrinology & Infertility, 8th Ed, 2011.
Testosterone Total vs Hirsutism Score
Mayo Clinic specific testosterone assay
RS Legro et al, Total Testosterone Assays in Women with Polycystic Ovary Syndrome: Precision and Correlation with Hirsutism, J Clin Endocrinol Metab. 2010; 95: 5305–5313
Hirsutism Score
2.6 nmol/L
4.5
Testosterone
Diagnosis of Hirsutism
• Isolated mild - no request for testosterone• Moderate / severe, sudden onset, progressive
– Especially associated with: menstrual irregularity, infertility, central obesity, acanthosis nigricans, rapid progression, clitoromegaly
• Testosterone: day 2 - 5• Normal: no further tests• Rapid progression or virilisation:
– Consider androgen secreting tumour
Martin, Evaluation and treatment of hirsutism in premenopausal women. J Clin Endocrinol Metab: 93 (4), 1105-1120, 2008
Hirsutism, Amenorrhoea
• Hirsutism occurs most commonly with PCOS• Initial test:
– Testosterone total: day 2- 5, morning• Testosterone free
– adds no further diagnostic information– unnecessary test
Martin KA et al DIAGNOSIS AND EVALUATION OF WOMEN WITH PREMENOPAUSAL HIRSUTISM J Clin Endocrinol Metab: 93 (4), 1105-1120, 2008
Hirsutism, Amenorrhoea
High testosterone or progression
• If Testosterone total > 4.5 nmol/L– Lab request DHEAS, Testosterone free
• Or Rapid progression hirsutism, virilisation– Consider androgen secreting tumour– Request
• Testosterone free• DHEAS
Martin KA et al DIAGNOSIS AND EVALUATION OF WOMEN WITH PREMENOPAUSAL HIRSUTISM J Clin Endocrinol Metab: 93 (4), 1105-1120, 2008
Hirsutism, Virilisation, Amenorrhoea
Adult onset CAH is not an issue• Adult onset CAH, is NOT adrenal insufficiency,
normal cortisol• Consider if: early onset hirsutism or
ethnic origin is:– Mediterranean, Slavic, Ashkenazi Jewish
• If presenting with hirsutism alone– Anti-androgen therapy equivalent to
glucocorticoid therapy
• Diagnosis: day 2 – 5, morning
17 OH progesterone
Hirsutism, Virilisation, Amenorrhoea
Androstenedione is not necessary
• Commonly elevated• No diagnostic value over testosterone• Used: Diagnosis or management CAH
Androgen secreting tumours of adrenal or ovary
Ovarian Cycle
Progesterone
• Regular cycles: ovulation likely• Monitor pituitary-ovarian axis to confirm
ovulation: • Request: Midluteal progesterone on day 21
if 28 day cycle
• If midluteal progesterone: > 25 nmol/L:- Consistent with ovulation- No further hormone tests required
• Irregular cycles – repeat progesterone weekly• Require progesterone,
7 days pre onset menses
Infertility or Subfertility - 1
• If day 21 progesterone < 25 nmol/L
• Then repeat twice:- Midluteal progesterone - on day 21 if a 28 day cycle
Infertility or Subfertility - 2
Infertility or Subfertility – 3
• If Progesterone < 25 nmol/L after 3 cycles
• Request on day 2 - 5: – FSH, LH– Prolactin– Testosterone– Oestradiol– Consider TSH
Use of Serum Progesterone
• To determine– If ovulating – Specialist use if possible risk
• Miscarriage• Ectopic pregnancy
Thought to be Post Menopausal. Now pregnant
FSH & LH levels vary
Menopausal Symptoms + Oligo- or Poly-Menorrhoea
• Result: FSH > LH, FSH >30, Age <45Biochemically consistent with premature ovarian failure
• Result: FSH > LH, FSH 10 – 30, Age >45Consider early stage of perimenopause
• Result: FSH > LH, FSH 10 – 30, Age <45Consider early stage of premature ovarian failure
Menopausal Symptoms + Oligo- or Poly-Menorrhoea
Peri-Menopause - 1
• FSH fluctuates markedly • History basis of diagnosis. • Therapeutic trial HRT• No place assays: oestradiol, progesterone
• Thyroid disease symptoms may mimic
menopausal symptoms
Peri-Menopause – 2
Request FSH if• Not on HRT, oestrogen pill• Hysterectomy with ovarian conservation• Menstrual bleeding
• FSH on day 2 – 5–FSH > LH–Raised > 10 mIU/L–Indicates diminished ovarian response
• Request:- FSH, LH- Prolactin- Testosterone- Oestradiol
Oligo- or Poly-MenorrhoeaNO Menopausal Symptoms
The Toilet of Venus 1650Venus -
Diego Velazquez
Recommendations for requesting - 1
• Primary Amenorrhoea:– FSH, LH
• Secondary Oligo-, Poly-, A-menorrhoea :
– FSH, LH, Prolactin, Testosterone total, Oestradiol
• Hirsutism, Polycystic Ovarian Syndrome:– Testosterone total on day 2 - 5
• Menopause atypical:– FSH, LH on day 2 - 5
Recommendations for requesting - 2
• Galactorrhoea– Prolactin on day 2 - 5, after 12 midday
• Infertility:– Progesterone day 21
Dysfunctional Uterine Bleeding• Menorrhagia• Intermenstrual or post coital • Abdominal and pelvic examination • FBC: exclude anaemia• HCG: Exclude pregnancy / trophoblast• Consider TSH if symptoms or signs• No other hormone investigations• History: consider clotting disorder
Dysmenorrhoea: Laboratory tests not necessary
Post Pill AmenorrhoeaWeight Loss
Hypopituitarism
• Low– LH, FSH– Oestradiol
Libido Loss• Common• Tests only if indicated by history &
examination• Weak correlation with testosterone,
DHEAS, androstenedione, oestradiol, FSH, prolactin
• Rare causes consider: acromegaly, Cushing's syndrome, CAH, adrenal insufficiency
Hypothyroidism increases Prolactin
Amenorrhoea: PrimaryFailure to establish menstruation
• Absent by 13 years- Without secondary sexual development• Absent by 16 years
- With secondary sexual characteristics
• Family history: Consider watchful waiting• Request: FSH, LH
- Raised: Karyotype: 45 XO Turner syn46 XX Premature ovarian failure
- Low: Constitutional delayConsider: anorexia
exerciseillnesscoeliac diseasehypothalamic/pituitary
- Intermediate: Anatomical - ultrasound
Amenorrhoea: Primary
Secondary sexual characteristicsAbsent 13y
• Absent/abnormal then karyotype:- 46 XX Mullerian agenesis- 46 XY Androgen insensitivity
• Present + no outflow obstruction- As for 2o amenorrhoea
Amenorrhoea: Primary
Secondary sexual characteristics Present by 16 yearsUltrasound uterus