case history, physical examination, investigations The Question behind the Question ???? Clinical methodology;

Oestrogen Secondary sexual characteristics Endometrial Proliferation Systemic effect → Bone → Liver → CNS → Skin

Progestrone Secretory endometrium Systemic effects

Testosterone Androgenic effect → Hair, acne → Larynx → Clitoris → Muscle mass Libido

Specific Conditions PCOD Kallman Syndrome Turner Syndrome Testicular Feminisation Cushing Syndrome Cranio Pharyngioma Anorexia Nervosa

Amenorrhoea Primary → If growth and sexual development are normal → no menses by 16 years Secondary → In a woman who has menstruated normally before → no menses for 6 months

Testicular Feminisation No spermatogenesis No axillary / pubic hair Tests; abdomen / inguinal canal Mechanism; Androgen Insensitivity Genotype; 46XY Phenotype; Female Normal testosterone production BUT

Testicular Feminisation Normal growth Large breasts Tall Underdeveloped female genitalia No uterus Rudimentary tubes Note → Risk of gonadal malignancy → Psychology Labia Vagina

CAUSES OF HIRSUTISM IDIOPATHIC ETHNICITY PCOS CUSHING SYNDROME LATE ONSET CAH ANDROGEN SECRETING TUMOUR ECTOPIC ACTH SECRETION DRUGS

DEPENDS ON CAUSE PSYCHOLOGICAL SUPPORT DIET COSMETIC HORMONAL MANIPULATION SURGICAL STEROIDS MANAGEMENT OF HIRSUTISM

Suppression of Cortisol Production by Dexamethasone Low Dose Dexamethasone High Dose Dexamethasone Normal womanSuppression No Suppression Ectopic ACTH production Pituitary dependent Cushing Syndrome

IF serum testosterone > 5 nmol/L Androgen secreting tumour until proven otherwise

Polycystic Ovarian Disease Clinical Biochemical Ultrasound DIAGNOSTIC CRITERIA

KEY CONCEPTS IN INFERTILITY Definition Human Rights Charter Causes, epidemiology, prevalence Difficulties in Legal adoption Primary, secondary, tertiary care Basic Semenology Assessment of ovulation Assessment of tubal patency Assisted reproduction Role of tubal surgery

Tubal Patency Tests Lap and dye HSP

Semen Analysis Volume 2-6ml Count × 10 6 /ml Motility > 50% Morphology > 50% must be normal ?Leucocytes ? Clumping Normal Values

ET/EPT The primary indication for The treatment of moderate and severe vasomotor symptoms systematic use of ET/EPT

Use of local ET Moderate and severe symptoms of vulval and vaginal atrophy

Use of progesterone Endometrial protection from ET

CC/EPT CS/EPT CC/EPT or CS/EPT regimens are appropriate.

There is insufficient evidence at the present time regarding endometrial safety to recommend the use of other regimens using progesterone. No ET or EPT regimen should be used for the primary or secondary prevention of coronary heart disease or cerebrovascular accident. The effect of ET on coronary heart disease and cerebrovascular accident is not yet clear. The risk of breast cancer probably increases with the use of EPT beyond five years duration. Progesterone appears to contribute to the adverse effect of HT on the risk breast cancer.

Definitive evidence for ET and EPT efficiency postmenopausal osteoporosis osteoporotic fractures postmenopausal osteoporosis osteoporotic fractures Reduce risk of

COMMITTEE ON SAFETY OF MEDICINES Review of the evidence regarding long-term safety of HRT October 2004

HRT advice for prescribers For the treatment of menopausal symptoms the benefits of short-term HRT are considered to outweigh the risks in the majority of women. Each decision to start HRT should be made on an individual basis with a fully informed woman.

In all cases, it is good practice to use the lowest effective dose for the shortest possible time and to review the need to continue treatment at least annually. This view should take into account new knowledge and any changes in a women’s risk factors and personal preferences. For postmenopausal women who are at an increased risk of fracture and are aged over 50 years, HRT should be used to prevent osteoporosis only in those who are intolerant of, or contraindicated for, other osteoporosis therapies.

Women who are receiving HRT for their menopausal symptoms will benefit from the effect of HRT on osteoporosis prevention whilst on treatment. Healthy women who have no menopausal symptoms should be advised against taking HRT as the risks outweigh the benefits.

HRT does not prevent coronary heart disease or a decline in cognitive function and should not be prescribed for these purposes. HRT remains contraindicated in women who have had breast cancer.

For women without a uterus, oestrogen-only therapy is appropriate. For women with a uterus, oestrogen plus progestogen is recommended. However, women should be fully informed of the added risk of breast cancer and be involved in the decision-making process.

ITEM 1The woman is aged 45 years, has noticed the growth of facial hair over the previous 6 months and has been amenorrhoeic for the last 3 months. She has a deep voice and appears to have a fine tremor. The results of ultrasound examination of the pelvis are normal, the serum testosterone is 6 nmol/l, serum dehydroepiandrosterone sulphate is elevated at 20 micromol/l, urinary free cortisol output is normal, serum 17 alpha hydroxy progesterone is well within the normal range and the serum FSH and LH are within the normal premenopausal range. A Androgen secreting adrenal tumourANSWER

ITEM 2The woman is aged 24 years and is worried by hirsutism which she says developed rapidly over the last 3 months. She has noticed that her skin is more “oily” and has been amenorrhoeic for ? 2 months. Ultrasound examination of the pelvis shows the presence of a left adnexal mass with a diameter of 5 cm, the lesion is possibly part of the left ovary but the view is partly obscured by gas in the bowel, the right ovary is not visualised and the uterus is normal. The serum testosterone is 6 nmol/l. Serum dehydroepiandrosterone sulphate, serum 17 alpha hydroxy progesterone and urinary free cortisol are well within their normal ranges. The serum FSH is greater than serum LH but both are within the normal premenopausal range. B Androgen secreting ovarian tumourANSWER

ITEM 3The woman is aged 34 years, complains of increased facial hair growth, has a 6 month history of oligomenorrhoea, has a long standing history of mild hypertension and has recently noticed that she gets tired at work as a typist. Serum testosterone, serum dehydroepiandrosterone sulphate, serum 17 alpha hydroxy progesterone and serum urea and electrolytes are normal. The 24 hour urinary cortisol output is 1200 nmol/l with failure of suppression on low dose dexamethasone (0.5 mg 4 times p.o.) and high dose dexamethasone (2 mg 4 times daily p.o.) D Ectopic ACTH productionANSWER

ITEM 4A 30 year old woman is concerned about mild hirsutism, acne and irregular menstrual bleeding. The salient features on examination were mild facial hirsutes, facial acne and her BMI was 36. Ultrasound examination of the pelvis was incomplete with poor visualisation of the ovaries but increased endometrial thickness was noted. The uterus appeared to be normal. The serum LH was greater than serum FSH and the serum testosterone, serum dehydroepiandrosterone sulphate, serum 17 alpha hydroxy progesterone and serum urea and electrolytes were well within the normal range. F Polycystic ovarian syndromeANSWER

The End Thank you very much. S. J. Duthie