Hyper-androgenism, hirsutism, PCOS Flashcards
Which androgens does the ovary produce?
Testosterone, androstenedione and dehydroepiandrostendione (DHEA)
Which androgens does the adrenal gland produce?
Dehydroepiamdrpsterone sulphate (DHEA-S) with androstendione and DHEA
(Very little testosterone)
Do androstenedione and DHEA have androgenic activity?
No, converted to testosterone in peripheral tissues
What % testosterone produced from ovaries?
2/3, normally overproduction caused by increased ovarian function
What % of testosterone is bound? To which molecules?
85% sex hormone binding globulin - inactive
10-15% albumin - active
1-2% free - active
Which hormone converts testosterone to its active form dihydrotestosterone?
5 alpha reductase, increase in hormone → androgen excess
List causes of hyper androgenism
1) Exogenous - testosterone/anabolic steroids/danazol/androgenic steroids
2) Ovarian - PCOS/stromal hyperthecosis, ovarian tumours (sertoli, hilus cell, krenkenburg)
3) Adrenal - tumour, cushings, adult onset adrenal hyperplasia
4) Androgen excess in pregnancy
5) Idiopathic hirsutism - increased 5-a reductase
6) Abnormal gonadal/sexual development
If rapidly progressive hirsutism and virilisation, what should be the concern?
Androgen secreting tumour
What questions should be asked in history for high androgen?
Note timing of onset and rate of progression - puberty / pregnancy; rapid progression suggestive of adrenal / ovarian tumour
History of virilisation - reduction in breast size, deepening of voice, clitoral enlargement, change in physique, male pattern baldness, hair-loss
Hirsutism - onset, progression, psychological impact
Mood change - change in libido, aggression
Other symptoms - menstrual irregularity, acne, infertility
Exclude iatrogenic, exogenous androgens
Family history - late onset congenital adrenal hyperplasia
What should be assessed for in clinical examination for hyper-androgenism?
BP - hypertension
Hirsutism - grade using the Ferriman-Gallway system
Acanthosis nigricans
Identify signs of virilisation and exclude abnormalities of the external genitalia
Identify signs of Cushing’s syndrome - plethora, moon face, increased pigmentation, central obesity, hypertension, striae, proximal muscle wasting, glycosuria
Abdominal and pelvic examination for abdomino-pelvic mass
During Ix for hyper-androgenism, which androgens suggest which source?
Source of androgen
High testostone = ovarian
Very high testosterone= tumour
Is suspecting Cushing syndrome, what test to order?
Overnight dexamethasone suppression test
For Late onset CAH what test.
ACTH stimulation test, increase 17 hydroxyprogesterone
What imaging should be ordered to Ix hyper-androgenism?
Pelvic USS - ?PCO or tumour
Abdominal CT/MRI - adrenal tumour
Any other test for hyper-androgenism?
Consider SHBG, androstenedione, free adrogen index
If virilisation → karyotype
Consider lipids, OGTT
What is the treatment for late onset CAH
Glucocorticoids
What is manamgnet for stromal hyperthecosis?
TAH + BSO
Who does ovarian hyperthecosis present in?
Postmenopasual women
Severe hyperandrogenism and insulin resistence (T2DM, CVD)
Which cancer do you need to consider in patients with ovarian hyperthecosis?
Endometrial cancer, testosterone is converted into oestrogen, risk endometrial hyperplasia, carcinoma
What would be seen in investigations for ovarian hyperthecosis?
High levels androstenedione
DHEA-S normal
USS: BL enlarged ovariaes
Definition of hirsutism
Terminal hair on body of women in same pattern/sequence seen in post pubertal male
Causes of hirsutism?
1) Exogenous / iatrogenic androgens - testosterone, anabolic steroids, androgenic progestogens, danazol
2) Increased ovarian androgens - Polycystic ovary syndrome / stromal hyperthecosis / ovarian tumours (Sertoli-Leydig cell tumours, Hilus cell tumours
3) Adrenal - tumours, Cushing’s syndrome, adult onset congenital adrenal hyperplasia
4) Androgen excess in pregnancy - luteoma
5) Idiopathic hirsutism - due to increased 5-alpha reductase activity in pilosebaceous unit
6) Abnormal gonadal / sexual development
7) Drugs - phenytoin, cortisone, minoxidil, diazoxide, cyclosporin A - alter the texture and extent of hair growth the pattern is non-androgenic and is referred to as hypertrichosis.
What grading system if used to score hirsutism?
Ferriman-Gallway grading system
0 (no terminal hair)
4 score at 11 sites
How does weight loss help treat hirsutism?
Reduced peripheral conversion androstenedione to testosterone
What physical methods can be used to treat hirsutism?
Bleaching
Shaving
Electolysis
What pharmacological methods can be used to treat hirsutism?
COCP
Medroxyprogesterone
Spironolactone
Flutamide - non steroid anti-androgen, check LFT
Finasteride - 5 alpha reductase inhibitor - needs effective contraception
Ketoconazole
Topical treatment for hirsutism?
Elfornithine hydrochloride (VANIQA) - improvement not seen until 4-8 weeks, can be used on face
What is the Rotterdam Criteria for the Dx of PCOS?
Must 2 of the following + exclusion of other causes:
1) PCO - >12 peripheral follicles or >10 cubic cm ovarian volume
2) Oligo-anovulation
3) Clinical/biochemical hyperandrogegism
What baseline bloods would you order for ?PCOS
TFT
Prolactin
Free androgen index
If clinical hyperandrogegism:
Total testosterone
17-hydroxyprogesterone
What is the free androgen index?
(Total testosterone/SHBG) x 100
How common is PCOS
Most common female endocrine abnormality
6-7% reproductive years
How common is PCO?
16-33% asymptomatic women
Biochemical changes PCOS
What would you see in androgens?
Raised, testosterone and androstenedione (ovarian hyper secretion)
50% also have raised DHEA-s (adrenal androgen)
Biochemical changes PCOS
What would you see in oestrogens?
Increased free estradiol/oestrone (peripheral conversion from androstenedione)
Biochemical changes PCOS
What would you see in SHBG?
Decreased SHBG, less production in the liver, increased biologically active androgens/oestrdiol
Biochemical changes PCOS
What would you see in prolactin?
Mildly raised
Risk of adult onset diabetes by age 40 with PCOS?
40%
Management of PCOS
Weight loss
COCP (Low androgen progesterone or cryproterone) or Medroxyprogesterone
BP/GDM/Cholesterol controll
If PCOS resistant to clomiphene indiction, what are the options?
GnRH therapy
Lap Ovarian drilling
How common is normalisation of serum androgens and SHBG after Lap ovarian drilling?
60% for up to 20 years
What skin condition can arise due to diabetes in PCOS?
Acanthosis nigricans
How to treat mild acne?
treat with topical agents such as azaleic acid, benzoyl peroxide, retinoids (contraception required) or antibacterial agents such as clindamycin 1% or erythromycin 2%.
How to treat severe acne?
Consider COCP (use one with non-androgenic progestogen / cyproterone acetate)
Isotrentinion
How long before starting isotrentinion should contraception be started?
1 month before strarting and 1 week after
At what level of free testosterone should you consider androgen secreting tumour?
> 5 or 2 x upper range
What is the definition of metabolic syndrome?
3 of the 5 following criteria:
1) Abdominal obesity
2) Hypertriglyceridemia
3) Low HDL cholesterol
4) Hypertension
5) High fasting gluovse
What os the most important risk actors for metabolic syndrome?
BMI
RR 1.89 per 4.7 kg
treatment for metabolic syndrome?
Increased exercise
Weight loss
Healthy diet
Treating hypertension / hypercholesterolaemia
Treating type II diabetes
What medical treatment for anovulatory infertility due to PCOS?
Clomifene citrate 50mg OD, 5 days from early menstrual cycle
USS monitoring
Max 6 months
or
Metformin
USS not required
GI upset
or
Letrozole
What are second line treatments of anovulatory infertility due to PCOS?
Laproscopic ovarian drilling
or
Gonadotrophin ovulation induction, S/C injections 10-20 days per cycle
What are third line treatments of anovulatory infertility due to PCOS?
IVF
