1. Clinical indications for androgen assays in gynaecology
Petra De Sutter
Div. Reproductive Medicine
UZ Gent

2. Androgens and women Source of androgens: Function? Which?
Ovarian theca and stromal cells <LH control
Adrenal cortex
Peripheral (< precursors)
Function?
Estradiol production (aromatisation in granulosa cells <FSH control)
Sex drive, muscular mass, etc…
Which?
DHEA(S) > A’dione > Testo-DHT
Postmenopauzal:
A’dion mainly adrenal source

4. 17-α-hydroxylase
desmolase

8. Oorzaken van androgeentekort bij de vrouw
1.Verminderde androgeenproductie
In ovaria: - normale veroudering
- bilaterale ovariëctomie
- radiotherapie
- chemotherapie
GnRH-agonisttherapie
In bijniercortex: - normale veroudering
- primaire/secundaire bijnierschorsinsufficiëntie
- bilaterale adrenalectomie
In ovaria en bijniercortex: panhypofysaire insufficiëntie

9. Illustration of the 50% parallel decrease in serum DHEA, DHEA-S, and testosterone between the ages of 21 and 40 years in healthy women

11. Oorzaken van androgeentekort bij de vrouw (vervolg)
2. Verhoogde binding van circulerende androgenen aan SHBG → verlaagde vrije androgeenfractie:
- oestrogeentherapie
- (hyperthyreoïdie)
3. Gestoorde androgeenreceptorwerking:
- aangeboren volledige of partiële androgeeninsensitiviteit
- inname van androgeenreceptorblokkeerders: cyproteronacetaat, spironolacton, flutamide

12. De vrouwelijke seksuele respons: het biopsychosociaal model (R.Basson)
Oxytocine ??
Oestrogenen
Androgenen
Emotionele
intimiteit
motivatie voor + +
Emotionele en
fysieke tevredenheid
Spontane seksuele honger (drive)
Seksuele
stimuli
Zin in seks
& verdere arousal +
Arousal +

13. Female androgen insufficiency: Princeton consensus (Fertil Steril 2002;77:660-5)
Symptomen: - verminderd welbevinden en neerslachtige stemming
- blijvende onverklaarde vermoeidheid
- verstoorde seksuele respons (libido)
Omdat oestrogenen ook een invloed hebben op stemming en seksuele respons, kan de diagnose alleen gesteld worden bij vrouwen met adequate oestrogenisatie
Vrije testosteronwaarde ≤ 25ste percentiel van normale waarden bij vrouwen tussen 20 en 40 jaar

14. Classification of Female Sexual Dysfunction*
Sexual desire disorders
Hypoactive sexual desire disorder Sexual aversion disorder
Sexual arousal disorder
Orgasmic disorder
Sexual pain disorders
Dyspareunia Vaginismus
Other sexual pain disorders
*Each disorder is subtyped as lifelong versus acquired, generalized versus situational, and as to etiologic origin (organic, psychogenic, mixed, unknown).

15. Androgen excess Hyperandrogenism (virilisation) Cycle disturbances
Acne
Hirsutism
alopecia
Cycle disturbances
PCOS

16. HAIR-AN syndrome Hyperandrogenism Insulin resistence
Acanthosis nigricans

17. Hyperandrogenism
= any clinical or laboratory evidence of androgen excess in women.
Most common clinical presentation of hyperandrogenism in reproductive-aged women is hirsutism or acne with or without evidence of anovulation such as oligo- or amenorrhea or dysfunctional uterine bleeding.
Elevated blood levels of androgens without clinical symptoms is referred to as cryptic hyperandrogenism.
Hirsutism = presence of course terminal hairs in androgen-dependent areas on the face and body in women >< hypertrichosis =excessive growth of thin vellus hair at any body site (usually familial or associated with anorexia nervosa or thyroid dysfunction, or with medications such as phenytoin, minoxidil or cyclosporin.
Hirsutism affects 2-10% of women between 18 and 45
Source of psychological discomfort
Scored by Ferriman-Gallwey score

19. Causes of Hyperandrogenism
Common
Polycystic Ovary Syndrome
80%
Idiopathic Hirsutism
15%
Uncommon
Late-Onset 21-Hydroxylase Deficiency
1-5%
Rare
< 1%
Steroidogenic Enzyme Deficiencies
3b-hydroxysteroid dehydrogenase
17-ketosteroid reductase
aromatase
Androgen Secreting Tumors of Ovary or Adrenal
Ovarian Hyperthecosis (a PCOS variant)
Other Endocrine
Hyperprolactinemia
Cushing syndrome
Defects in cortisol metabolism
Acromegaly

20. Evaluation of Hyperandrogenism
History
Onset
Progression
Onset at menarche suggests PCOS, idiopathic hirsutism or 21-hydroxylase deficiency. Onset distinct from menarche suggests tumor.
Rapid progression of hirsutism or other symptoms suggests tumor
Physical Examination
Hirsutism and acne
Virilization
PCOS or idiopathic hirsutism
Ovarian or adrenal tumor, hyperthecosis
Laboratory Tests
Total and free testosterone
17-hydroxyprogesterone
Prolactin, TSH
Confirm hyperandrogenism, rule out tumor
Rule out mild 21-hydroxylase deficiency. Perform ACTH stimulation test in patients of Askenazi Jewish descent
In all patients with oligo-amenorrhea or dysfunctional bleeding
Imaging
Transvaginal ultrasound
CT of adrenal glands
Confirm polycystic ovaries, rule out ovarian tumor
If ovarian ultrasound is normal and tumor is suspected

21. PCOS Validity of Rotterdam consensus? heterogenous disease
5-10 % of all adult women
20 % of all infertile women
80-90% of all anovulatory women
criteria for diagnosis (2 out of 3):
PCO image on ultrasound
increased androgens (clinically / chemically)
irregular cycles
Validity of Rotterdam consensus?

22. PCOS PCO (20%) ≠ PCOS (5-10%) increased androgens
often (but not always!):
obesity
insulin resistence (cave diabetes!)
increased LH and LH/FSH
PCO (20%) ≠ PCOS (5-10%)
increased androgens
< adrenal, ovary
acne, hirsutism
irregular cycles -> infertility

23. cameleon lab: symptoms: hyperandrogenism: 30-50% increased LH: 40-50%
irregualr cycles: %
amenorrhea: %
hirsutism: %
obesity: %
acne: %
infertility: %
lab:
hyperandrogenism: %
increased LH: %

24.                                     
Normal ovary PCO ovary

27. Prevalence genetic factors: racial factors families, twins
insulin? Hormone receptors?
exogeneous factors
racial factors
Genetic? Food? Surroundings?
Asian > mediterranean > Caucasian women

28. Short term problems during pregnancy obesity, acne and hirsutism
-> cosmetic problem, psychologic problems, low self image, depression
irregular cycles
-> infertility
during pregnancy
increased risk for miscarriage
increased risk for pregnancy diabetes and hypertension

29. Long term health risks obesity insulin resistence -> diabetes
-> cariovascular disease, hypertension, myocardial infarction
insulin resistence -> diabetes
metabolic syndrome or syndrome X
-> obesity, hypercholesterolaemia, atherosclerosis, diabetes
irregular cycles
-> endometrium hyperplasia and cancer

31. Importance of obesity obesity -> does NOT lead to PCOS
women with PCOS who also are obese have an increased chance to develop symptoms: obesity worsens PCOS !
weight loss therefore ameliorates PCOS symptomatology

32. Treatment weight loss (>5% often normalizes cycle regularity)
OCS (cycle reg, decreasing androgens)
typically Diane 35 (CA) or Yasmin (drosperinone)
if child wish: hormonal stimulation
if hirsutism: OCS + CA or cosmetic
metformin ??? Only if IR
dexamethasone >< adrenal androgens
(statins >< lipid disturbances, ovarian androgens)

33. Life style modification !
TABLE 1. Clinical Impact of Lifestyle Management in PCOS From:   HOEGER: Clin Obstet Gynecol, Volume 50(1).March

35. Thank you for your attention