Approach to secondary amenorrhoea Definition •Secondary amenorrhoea refers to absence of menses...
Transcript of Approach to secondary amenorrhoea Definition •Secondary amenorrhoea refers to absence of menses...
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Problem solving - Approach to
secondary amenorrhoea
Dr Marilyn Lee
KTPH
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Objectives
• Causes of secondary amenorrhoea
• Evaluation
• Management
• HRT vs OCP
• Learning points
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• 26/F
• Amenorrhoea 8 months
• Not sexually active
• Menarche age 13, regular until a year ago.
• History of migraines – no regular meds
• No hot flushes, vaginal dryness
• No hirsutism/acne/scalp hair loss
• BMI 20 kg/m2
• No galactorrhoea
• Clinically euthyroid
• Bp 116/74
FT4 17.5 pM, TSH 2.4 mu/L
LH 3.0 mu/L, FSH 4.2 mu/L
Testosterone – within normal limits
Prolactin – within normal limits
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Definition
• Secondary amenorrhoea refers to absence of
menses for over 3 months in women who
previously had regular menstrual cycles, or 6
months in women who had irregular menses
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Introduction
• The menstrual cycle is susceptible to external
influences, hence, missing a single period is rarely
important
• In contrast, prolonged amenorrhoea may be the
earliest sign of a decline in general health or signal an
underlying medical problem (eg hyperthyroidism)
• Always exclude pregnancy
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• HYPOTHALAMIC-
PITUITARY-OVARIAN
AXIS
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Hypothalamic dysfunction
-Functional hypothalamic amenorrhoea
-Inflammatory/infiltrative disease
-Tumour
-Traumatic brain injury
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Pituitary disease
-hyperprolactinemia
-empty sella
-other sellar masses
-other diseases of the pituitary
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Ovarian (PCOS, POF)
Uterine (Asherman)
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Approach – history and examination
• Hypothalamic – Eating disorders, high intensity exercise, stress, chronic
severe illness, traumatic brain injury
• Pituitary – Galactorrhoea, drugs
– Symptoms/signs of cushing’s or acromegaly
• Ovarian – Symptoms of oestrogen deficiency
– Hirsutism/acne/scalp hair loss*
• Others – Symptoms of thyroid dysfunction
– Virilization
– Uterine instrumentation
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Diagnostic evaluation
• Laboratory investigations
– Gonadotropins, TFT, prolactin
– Consider testosterone, 17OHP
• USS pelvis
– Polycystic ovaries?
– Endometrial thickness
• Progestin withdrawal
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History and examination
hCG, TFT, prolactin
abnormal Evaluate for thyroid dysfunction,
hyperprolactinemia FSH
Premature ovarian insufficiency high
Progestin withdrawal
Oestrogen replete
PCOS (+/- pelvic USS)
Oestrogen deplete
Withdrawal bleed No withdrawal bleed
Combined oestrogen and progestin
FHA
Hypothalamic-pituitary
Anatomic defects
*additional tests if clinically indicated Testosterone, 17OHP, ONDST
No withdrawal bleed Withdrawal bleed
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• 26/F
• Amenorrhoea 8 months
• Not sexually active
• Menarche age 13, regular until a year ago.
• History of migraines – no regular meds
• No hot flushes, vaginal dryness
• No hirsutism/acne/scalp hair loss
• BMI 20 kg/m2
• No galactorrhoea
• Clinically euthyroid
• Bp 116/74
FT4 17.5 pM, TSH 2.4 mu/L
LH 3.0 mu/L, FSH 4.2 mu/L
Testosterone – within normal limits
Prolactin – within normal limits
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Question
Which of the following statements is true?
1. This is not PCOS because testosterone level is not elevated
2. A normal BMI excludes hypothalamic amenorrhoea
3. As blood tests are all normal, no further evaluation is required
4. An USS showing a thin endometrial lining makes PCOS less likely
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Rotterdam Criteria
• 2 out of 3:
– Oligo/amenorrhoea and/or anovulation
– Hyperandrogenism
– Polycystic ovaries on USS
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PCOS – An Endocrine perspective
High LH - ~ 40% - Marker for anovulation in lean women
High Testosterone - ~ 50% Marker for hirsutism
High Insulin - ~ 30% - Marker for oligomenorrhoea and T2DM
High AMH - ~ 70% - Marker of follicle count
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• US – polycystic ovaries, endometrial thickness
3mm, ovarian volume 8ml
• Further history – runner of 15-20km at least 3
times a week
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Question
What is the most likely diagnosis?
1. Polycystic ovarian syndrome
2. Functional hypothalamic amenorrhoea
3. Premature ovarian insufficiency
4. Non classic congenital adrenal hyperplasia
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Normal gonadotrophin amenorrhoea
Usually PCOS or Hypothalamic Amenorrhea (HA)
PCOS HA
Exercise program? Rare Common
BMI Any - usually > 21 Usually < 21
Androgen excess Common Rare
Suppressed LH Rare Common
Polycystic Ovaries >90% 20%
Endometrial thickness Rare < 5 mm < 5 mm
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Management
• Anovulatory cycles and oestrogen replete
– Progesterone every 2-3 months
– Eg Dydrogesterone 10mg BD x 1 week
• Oestrogen deplete
– Combined oestrogen and progesterone (either OCP
or HRT)
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Question
DEXA scan shows z score of -2.1 in both left hip
and lumbar spine.
Apart from advising her to reduce exercise, how
would you manage her?
1. OCP
2. HRT
3. Watch and wait
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HRT vs OCP
Progesterone
Oestrogen 21
28
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HRT REFERENCE SHEET
Sequential oestrogen and progesterone combinations Continuous
combined
Unopposed
oestrogen
Tablets Oestrogen Progesterone Tablets
Trisequens Oestrogen
1,2mg
Norethisterone Activelle
(1mg/0.5mg)
Estrofem
Femoston conti
1/5
Premarin
Progyluton Oestrogen 2mg Norgestrel Progynova
Patch (ug/24
hrs)
Femoston Oestrogen
1,2mg
Dydrogesterone Estraderm
MX (25,50)
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HRT REFERENCE SHEET Other oestrogens Type
Oestrogel Oestradiol Gel
Divigel Oestradiol Gel
Norethisterone Norethisterone 5mg Tablets
Provera Medroxyprogesterone
10mg
Tablets
Depot provera Medroxyprogesterone
150mg/3ml injection
Injection
Mirena Levonorgestrel
(20mcg/24hr)
IUS
Duphaston Dydrogesterone 10mg Tablets
Uterogestan Micronized progesterone
100mg
Capsules
Progesterone
injection
Progesterone 50mg/ml
(5-10mg daily)
Deep im injection
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Learning points
• Always exclude pregnancy
• Once thyroid dysfunction and hyperprolactinemia are excluded, FSH should be done to distinguish between a primary ovarian pathology vs other causes
• PCOS and HA are the commonest causes of anovulatory cycles.
• Differentiating between them may require a combination of history, examination, biochemical and radiological tests.
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References
• Deligeotoglu E, Athanasopoulos N, Tsimaris P, et al. Evaluation and
management of adolescent amenorrhoea. Ann N Y Acad Sci 1205:23-43,
2010
• Laufer MR, Floor AE, Parsons KE et al. Hormone testing in women with
adult onset amenorrhoea. Gynecol Obstet Invest 40:200-203, 1995
• Hendriks ML, Brouwer J, Hompes PG et al. LH as a diagnostic criterion
for polycystic ovary syndrome in patients with WHO II oligo/amenorrhoea.
Reproductive Biomedicine 16:765–771, 2008
• Dewailly D, Lujan ME, Carmina E et al. Definition and significance of
polycystic ovarian morphology: a task force from the Androgen Excess and
Polycystic Ovary Syndrome Society. Human Reproduction Update
20(3):334-52, 2014
• Conway G, Dewailly D, Diamanti-Kandarakis E et al. The polycystic ovary
syndrome: a position statement from the European Society of
Endocrinology. Eur J Endocrinol. 171(4):1-29, 2014
• Marilyn R Richardson. Current Perspectives in Polycystic Ovary
Syndrome. Am Fam Physician. 68(4):697-705, 2003