Download Female Reproductive Endocrinology

Female Reproductive
Endocrinology
Professor Ernest Hung Yu NG
Department of Obstetrics & Gynaecology
The University of Hong Kong
Outline
1.
Oligo-amenorrhea / amenorrhea
2.
Hyperandrogenism / Hirsutism
3.
Adolescent gynaecology
4.
Menopause
5.
Sexual health and contraception
Oligomenorrhea / Amenorrhea


Oligomenorrhea: reduction in the frequency
of periods where menstrual intervals may
vary between 6 weeks and 6 months.
Amenorrhoea: complete cessation of periods
for > 6 months.
 Primary amenorrhoea-- the absence of
spontaneous onset of periods by the age of 16
years.
 Secondary amenorrhoea-- the absence of periods
for 6 months or more when a patient has regular
periods before and 12 months or more when the
patient has irregular cycles all along.
Hypothalamic-pituitary-ovarian axis
Ovarian cycle

FSH is the key gonadotrophic
hormone for follicular
development

LH is important in
1. Supporting E2
biosynthesis
2. Selecting a dominant
follicle
Two-cell, two-gonadotropin
theory
Causes of amenorrhoea

Physiological
Pre-puberty, pregnancy, lactation and menopause

Pathological
Anatomical causes in the genital tract
Endocrine dysfunction
Hypothalamic-pituitary-ovarian axis
Others
Anatomical causes in the genital
tract

Congenital
 Absence of uterus (with or without absent vagina)
 Testicular feminization syndrome
 Outflow tract obstruction (imperforate hymen or
transverse vaginal septum)

Acquired
 Endometrial damage: traumatic (Asherman’s
syndrome), chronic endometritis (pelvic
tuberculosis), endometrial resection or ablation
 Cervical stenosis (extremely rare): surgical trauma,
infective
 Vaginal stenosis (extremely rare): chemical
inflammation
Endocrine dysfunction
Hypothalamic-pituitary-ovarian axis
 Ovarian
 Ovarian failure: genetic, autoimmune, after
surgery/chemotherapy/radiotherapy, galactosaemia and idiopathic
 Polycystic ovary syndrome

Pituitary
 Pituitary failure : adenoma, infarction (Sheehan’s syndrome), infection
(encephalitis), irradiation
 Hyperprolactinaemia : prolactinoma, primary hypothyroidism, chronic renal
failure, and drug-induced

Hypothalamic
 Congenital (Kallmann’s syndrome)
 Functional causes : weight loss, anorexia nervosa, excessive exercise,
psychological stress, debilitating illness

Others
 Thyroid disease
 Adrenal disease
Environment
Compartment IV
Central nervous system
Hypothalamus
GnRH
Compartment III
Anterior pituitary
Compartment II
FSH
LH
Ovary
Compartment I
Estrogen
Progesterone
Uterus
Menses
History

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Stress
Appetite & weight changes
Virilization
Headaches & visual
changes
Hot flushes
Galactorrhoea
Secondary sexual
characteristics
Growth spurt





Cyclical abdominal pain
Drugs
Symptoms of systemic
disease
Past health: TB, surgery to
uterus, postpartum
haemorrhage, radiotherapy
(cranial or pelvic)
Sexual activity and use of
contraception
Physical signs





Nutritional state
Body weight and
height
Secondary sexual
characteristics
Virilization/ hirsutism
Galactorrhoea




Thyroid gland
Visual field /
neurological sign
Sign of systemic or
endocrine disease
Pelvic examination
Amenorrhoea
•TSH
•Prolactin
•Progestational Challenge
Elevated TSH
Hypothyroidism
+withdrawal bleeding
Normal prolactin
Normal TSH
- withdrawal bleeding
Raised Prolactin
Anovulation
E and P cycle
+withdrawal bleed
-withdrawal bleed
FSH
End organ problem
Normal
High
Hyperprolactinaemia
Low
MRI
Hypothalamic
amenorrhoea
Ovarian failure
Management




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Establish a diagnosis and manage accordingly
Exclude serious/ life-threatening causes or
consequences
Management of menstrual and/or hormonal problem
Advise on future fertility potential
Sexual function
Prevent long term health problem: osteoporosis,
cardiovascular disease/ metabolic disease, endometrial
hyperplasia/ carcinoma.
Psychological issues
What is hyperprolactinaemia?

Elevated prolactin:
Female patients < 25 ng/ml (530 mIU/L)
Causes of hyperprolactinaemia

Pituitary disease
 Prolactinomas
 Microadenoma
 Macroadenoma
 Acromegaly
 Empty Sella syndrome
 Cushing’s disease
 Non-functional tumours
causing disconnection
hyperprolactinaemia


 Antipsychotics
 Antidepressants (SSRI, TCA,
MAOI)
 Antihypertensives (Methyldopa)
 Etc.

Other:
 Hypothyroidism
 Rare causes
 Chronic renal failure
 Cirrhosis
 Estrogen
 PCOS
 Oral contraceptive pills
Hypothalamic disease
 Craniopharyngiomas or other
tumours
 Infiltrative disease
 Irradiation
Drug-induced


Stress
Physiological
 Pregnancy & lactation

Idiopathic
Clinical symptoms

Anovulation
Amenorrhoea / oligomenorrhoea
Infertility
Osteoporosis
Galactorrhoea
 Pressure symptom:

Headache
Visual field defect (bitemporal hemianopia)
Investigations



Pregnancy test
Thyroid function tests
Imaging study of the
pituitary
 MRI
 CT scan with IV
contrast
Treatment options

Medical agents
Dopamine receptor agonists:
Bromocriptine
Cabergoline
Quinagolide
Inhibits pituitary prolactin secretion
Surgery
 Radiotherapy

Hyperandrogenism



Clinical: acne, hirsutism, male pattern baldness,
virilisation
Biochemical: reference ranges vary
In case of severe hyperandrogenaemia (e.g. total
testosterone > 5 nmol/l) or signs of severe hirsutism or
virilisation:
 17-hydroxyprogesterone to exclude late-onset congenital
adrenal hyperplasia,
 Overnight dexamethasone suppression test to exclude
Cushing’s syndrome
 Imaging (pelvis and adrenals) to exclude an androgensecreting tumour.
Hirsutism





Presence of excessive terminal hair in androgensensitive areas of the female body
The modified Ferriman–Gallwey score (mFG) proposed
by Hatch et al. (1981) has now become the gold
standard for the evaluation of hirsutism.
Inter-observer variation, population dependent
The actual prevalence ranges from 4.3 to 10.8% in
Blacks and Whites, but appears to be somewhat lower
in Asians.
No universal cut-off, mFG score > 8 in White & Blacks
Hirsutism
Aetiologies:
1.
PCOS
2.
Idiopathic hyperandrogenism (clinical / biochemical)
3.
Idiopathic hirsutism
4.
Non-classic CAH
5.
Androgen-secreting tumors
Investigations:

Testosterone, SHBG

Mid-luteal progesterone,

If anovulation: FSH, PRL, TSH, USG pelvis

Metabolic profile if PCOS

Imaging to exclude androgen-secreting tumours if significant
high testosterone (>5 nmol/l), rapid onset of symptoms or
virilisation
Escobar-Morreale et al, Hum Reprod Update 2012
Treatment of hirsutism
1.


Cosmetic measures
To remove terminal hair already present
bleaching, plucking, shaving, waxing, electrolysis,
laser therapy
Treatment of hirsutism
2.



Pharmacological therapy
Topical eflonithine cream
 Inhibitor of L-ornithine decarboxylase, an enzyme
essential in growth of hair follicle
 Slows facial hair growth in up to 70% of patients
To reduce androgen production / action
 Combined oral contraceptives with newer generation
progestogens / cyproterone
 Anti-androgens: cyproterone, finasteride, spironolactone
May take at least 6 months to 1 years to have clinically
observable effects
Escobar-Morreale et al, Hum Reprod Update 2012
Adolescent gynaecology

Congenital abnormalities of genital tract
 Ambiguous genitalia, imperforate hymen, vaginal septae,
uterine anomalies, Mullerian dysgenesis/agenesis,
gonadal dysgenesis

Puberty
 Physiology and chronology
 Precocious puberty
 Delayed puberty

Menstrual problems
Menopause

Physiology of the climacteric

Hormone replacement therapy
 Update in: Climacteric 15(3) (June 2012)

Non-hormonal therapy**

Osteopenia and osteoporosis

Premature ovarian failure
(Maclaran & Panay.
J Fam Plann Reprod Health Care 2011;37:35–42.)
Sexual and reproductive health

Fertility regulation
 Natural family planning (physical, Persona®)
 Barrier: condom, diaphragm, caps
 Spermicides
 Hormonal: oral, transdermal, subdermal**, injectable,
intrauterine**
 Male and female sterilisation, reversal of sterilisation
 Intrauterine device
 Emergency contraception
Sexual and reproductive health



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Termination of pregnancy (RCOG Guideline 2011**)
 Pre-procedure consultation/assessment, dating
 Choice of method (medical/surgical), procedure, risks
 STI screening and prophylaxis
Sexual health:
 STI screening, counselling and treatment
 Psychosexual problems: initial assessment & referral
Premenstrual syndrome
Remember: Counselling, psychosocial aspects & support,
consent & confidentiality
Contraception



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Contraceptive counselling (including sterilisation)
Contraception in special groups: adolescents,
perimenopausal, medical problems, high risk group for
poor sexual health
Non-contraceptive uses of hormonal contraceptives (COC,
POP, injectables, Mirena®)
More recent advances (may not be for examination!)
1. Natural estrogen-containing COCs
2. Hysteroscopic sterilisation