ILA- amenorrhoea

Question 1

What are the hormones involved in the Hypothalamicpituitary-gonadal-target organ axis?

Answer 1

GnRH from the hypothalamus –> LH and FSH from anterior pituitary –> oestrogen and progesterone from ovaries

Question 2

briefly describe the embryology of the genital tract?

Answer 2

Genital tract develops in the same way for both sexes, SRY gene differentiates it into male

Since no testosterone is produced the mesenteric ducts regress

Since there is no MIS the paramesonephric ducts produce oviducts, uterus and the upper third of the vag

The urogenital sinus forms the bublourethral glands and the lower 2/3rd of the vagina

Question 3

What is primary amenorrhoea?

Answer 3

no periods ever. Primary amenorrhoea can be diagnosed in female children by age 13 if no secondary sex characteristics, such as enlarged breasts and body hair, are present. If secondary sex characteristics are present, but menstruation is not, primary amenorrhoea can be diagnosed by age 16.

Question 4

What is secondary amenorrhoea?

Answer 4

where menstruation begins as normal but then stops for 6 plus months not due to natural causes eg lactation, pregnancy or the menopause

Question 5

What is oligomenorrhoea?

Answer 5

32 day plus between periods

Question 6

What are some causes of primary amenorrhoea in the absence of secondary sex characteristics?

Answer 6

Constitutional delay: short with pre-pubertal levels of GnRH and low steroids

Hypogonadotropic hypogonadism – (will have GnRH and low steroids)

Premature ovarian insufficiency

Low FSH and LH levels

Question 7

What are some causes of hypogonadotrophic hypogonadism?

Answer 7

Hypothalamic failure due to anorexia, stress, chronic illness, obesity
Tumour of hypopituitary glands
Kallmann’s

Question 8

What are some causes of premature ovarian insufficiency?

Answer 8

autoimmune eg thyroid, adrenal disease 
chromosomal causes eg Turner’s, fragile X 
chemo or radiotherapy 
oophorectomy 
infection

Question 9

What are some causes of primary amenorrhoea in the presence of secondary sex characteristics?

Answer 9

Malformation of the uterine duct
Androgen insensitivity syndrome- are phenotypically female but have male chromosomes- intersex
hyperprolactinaemia
Constitutional delay- may just reach a little later, ask about Fhx

Question 10

What are some physiological causes of secondary amenorrhoea?

Answer 10

pregnancy/ lactation/ menopause/ contraception

Question 11

What are some causes of secondary amenorrhoea?

Answer 11

Premature ovarian insufficiency (early menopause) 
Hypogonadotropic hypogonadism
Thyroid problems 
Hyperprolactinemia
PCOS- excess androgens 
Sarcoidosis 
Sheehan’s syndrome 
Ovarian carcinoma- can produce androgens 
Asherman's syndrome 
Cushing's - excess androgens

Question 12

What are some hypothalamic causes of amenorrhoea?

Answer 12

-stress, anorexia, weight loss or exercise

Question 13

What is Sheehan’s syndrome?

Answer 13

Caused by ischemic necrosis of pituitary gland due to severe PPH

Question 14

What is Asherman’s syndrome?

Answer 14

Cervical stenosis due to adhesions in uterine cavity that obstruct menstrual flow usually due to surgery

Question 15

What is Kallman’s syndrome?

Answer 15

A genetic disorder characterised by failure of secretion of gonadotropin-releasing hormone (GnRH)
Is caused by neurones failing to migrate from the nose region to the hypothalamus during fetal development . So GnRH, LH and FSH is low and therefore oestrogen is low.

Question 16

What investigations can be carried out for amenorrhoea?

Answer 16

History- Duration of amenorrhoea. Contraception, recent and current. Vasomotor symptoms. Galactorrhoea. Exercise habits. Stresses. Medication history. Past medical history.

O/E- BMI, Cushing’s and thyroid signs

Pregnancy test!!

FSH and LH (raised in ovarian failure, if short with high levels indicates Turner’s, normal height with low levels indicates constitutional delay or hypothalamic causes eg weight loss, stress, exercise)

Oestrogen levels

Prolactin

Serum free androgen index – raise in PCOS

Testosterone (slight raise indicates PCOS, big raise indicates androgen secreting tumour),

TFTs (low TSH can indicate pituitary failure, look for hypo/hyper thyroid)

Pelvic U/S (PCOS or congenital abnormalities)

Karyotype for Turner’s and androgen insensitivity syndrome

Look for illness if indicated

CT/MRI for tumour

Hysteroscopy for Asherman’s

Question 17

What is the management for amenorrhoea?

Answer 17

Hormone replacements eg HRT or OCP
fertility advice

Structural abnormalities may have surgery

Tumour do surgery/ RT

Management of patients with Turner syndrome includes growth hormone for short stature and also identifying and monitoring any associated cardiac, renal and thyroid abnormalities. Oral contraceptives should also be given. Fertility preservation through the cryopreservation of oocytes or ovarian tissue may be an option for some girls with Turner syndrome.

Bone protection due to associated low oestrogen levels

Question 18

What are the characteristics of Turner’s syndrome? (think CLOWNS)

Answer 18

Cardiac abnormaly - coarctation of the aorta
Lymphoedema
Ovaries not developed
Webbed neck
Nipples wide spaced
Short stature

also: don’t completely develop sex characteristics, infertile, kidney problems, low hairlines, koilonychia, eyes slant downwards, ptosis, strabismus (squint), amblyopia (lazy eye), ear infections

Question 19

Belinda Cochrane has been referred by her GP with the following letter: Dear Doctor Please see this lady who is having very infrequent periods. She is 32 years old and has had no previous pregnancies but would like to become pregnant. Her periods started at the age of 13 and have never been very regular. She started the combined pill at the age of 17 to regulate her cycle. She stopped the pill two years ago and has only had 2 or 3 periods each year with a very irregular pattern. Belinda is an accountant. She is generally healthy but has had problems with anorexia in the past and finds it difficult to maintain weight. She also has problems with facial hirsutism. Periods occur every three to four months.

2 Baseline investigations are: Random sample LH 7.1 IU/L FSH 4.5 IU/l Prolactin 425 pmol/L Progesterone 2 nmol/L TSH normal
What are the differentials?

Answer 19

May be due to stress/ weight loss – affecting the hypothalamic-pituitary axis
PCOS- oligomenorrhoea, hirsutism, acne, subfertility
Cushing’s
Congenital adrenal hyperplasia
hyperprolactinaemia

Question 20

What is the management for PCOS?

Answer 20

advise weight loss if needed, monitor for DM and high cholesterol, clomifene citrate or letrozole (induces ovulation for fertility), ovarian drilling (reduced steroid production), COCP (help with period regulation and unopposed oestrogen), cyproterone spironolactone, flutamide, finasteride (for hirsutism- anti-androgen)

Question 21

What is the most common cause of primary amenorrhoea? how does the mechanism work?

Answer 21

Turners syndrome
missing X chromsome means follicles are depeleted at an accelerated rate - menopause occurs before menarche
no rise in oest or prog from corpus luteum –> high LH and FSH

Question 22

What is the second most common cause of primary amenorrhoea? how does the mechanism work?

Answer 22

Mullerian agenesis

• -> mullerian duct doesn’t develop properly (uterus, vag and cervix may be absent or malformed/obstructed)
• > ovaries are normal so normal level of hormones

Question 23

Explain androgen insensitivity syndrome

Answer 23

biologically male (46XY) - but receptors don't respond to testosterone 
Have internal testes and absent female sex organs 
have female ext genitalia and seconday sex characteristics