Endocrine Disorders Affecting Reproduction Flashcards
What is the clinical application of GnRH secretion?
normally GnRH production is pulsatile
If continue GnRH is give, this downregulates FSH/LH
- can be used to time IVF cycles etc
What are the 3 categories of things that can go wrong with the HPGaxis?
- central pathology
- lack for section of LH/FSH
- hypothalamic/pituitary disease - Gonadal damage
- failure of germ cell production
- lack of sex steroid production - polycystic ovarian syndrome
What is the typical presentation of a female
Menstrual history - oligomennorhea - amennorhea - primary vs secondary Oestrogen deficiency - hot flushes, poor libido, dyspareunia Hirsutism, acne, androgenic alopecia Weight Galactorrhoea
What are the causes of amenorrhoea?
- pregnancy
Central causes - hypothalamic: anorexia, exercise, stress
- pituitary: hyperprolactinaemia, pit tumours
- hypogonadotrophic hypogondasim (failure of LH, FSH secretion)
Ovarian causes: - Turner’s
- Premature ovarian failure
Polycystic Ovarian Syndrome
Miscellaneous - thyrotoxicosis, chronic disease, local uterine problems
How can leptin affect the female reproductive system?
Congenital leptin deficiency
- Severe obesity and hyperphagia
Hypogonadotrophic hypogonadism
How is prolactin secretion regulated?
- synthesised by lactotrophs
- regulated of PRL different to the a. pituitary hormones
- negative regulation by tonic release of dopamine
What are the causes of physiological hyperprolactinaemia?
physical or psychological
post seizure
greater increase in women
PRL does have circadian rhythm with peak during sleep
- don’t examine breasts and then measure prolactin
What are the clinical features of hyperprolactinaemia?
- less apparent in post-menopausal women and men
- hypogonadism - oligo/amenorrhoea
- symptoms of low oestrogen
- ## galactorrhea
What are the pathological causes of hyperprolactinaemia?
- prolactinomas
- loss of inhibits effect of hypothalamus derived dopamine
- Drugs - dopamine antagonist e.g. phenothiazines, metoclopramide, TCAs, verapamil
- hypothyroidism link
What are the signs, symptoms and causes of primary ovarian insuffiency?
Amerrohea, oestrogen deficiency
Elevated LH, FSH
Causes:
- congenital e.g. turners
- autoimmune
- iatrogenic - chemo/radiotherapy, surgery
- mutations in FSH receptor galactossaemia, FMR1 gene permutation (fragile X)
What is the phenotype of a girl with Turner’s syndrome?
short stature streak ovaries webbed neck cubitis valgus congenital heart disease hypothyroidism lumphoedema
Describe autoimmune primary ovarian insufficiency
- often caused by autoimmune disease such as Graves, Addissons, diabetes
- POI often precedes addisions by 8-14 years
- mechanism is likely to be due to inflammatory infiltration of follicles and production of anti ovarian Ab, apoptosis and atrophy
- sharing of auto antigens between the ovary and adrenals amy explains the addissons link
What is the link between Fragile X permutation and POI?
- 1 in 200 females has the genetic change that leads to FXPOI.
- FXPOI accounts for about 4-6% of all cases of POI in women
- Mutuations in the FMR1 gene increase a woman’s risk of developing FXPOI
- FXPOI is inherited in an X-linked dominant pattern therefore one copy leads to the condition
How is Primary Ovarian Insufficiency diagnosed and managed?
- diagnosis on sera FSH and E2 levels (oestrogen)
- karyotyping and FMR-1 permutation analysis
- screening for autoimmune diseases
- AMH measurement is a good measure of ovarian reserve
- DEXA scan: risk of osteoporosis
- manage with oestrogen replacement - need progesterone added if still has uterus
What are the signs and symptoms of polycystic ovary syndrome
Aeitiology?
- oligoamenorrhoea
- hirsutism
- obesity
- infertility - anovulation
- polycystic ovaries on ultrasound
- hyperandrogegism: increased T, androstenedione (DHEA)
- increased LH/FSH ratio
Aeitiogloy = insulin resistance?
What is the Rotterdam Diagnostic Criteria for PCOS?
2/3 of the following:
- oligo/amenorrhea
- clinical or biochemical signs of hyperandrogenaemia
- polycystic ovaries
What is acanthosis nigricans?
- Often seen in PCOS
- dark skin markings, usually on neck
- marker of insulin resistance
What is hirsutism?
Male hormone dependent hair growth
- upper lip, chin, anterior neck, sideburn, breasts, pubic hair
What is a common score of hirsutism?
Ferriman Gallwey Score of Hirsutism
What are the risk of PCOS and pregnancy?
- oligo/amennorhea and infertile commonest clinical problem
- risk of gestational diabetes and pregnancy-related hypertension is ten times increased
- IVF: risk of hyperstimulation syndrome and subsequently fertilisation of more than one egg
PCOS - What do you need to treat and how?
Obesity, oligo/amennorhea
- metform, lifestyle modification, progesterone replacement, bariatric surgery
Anovulatory infertility
- metformin –> +climophene/IVF
Hirsutism
- yasmin, Vaniqua cream, cosmetic removal, spironolactone
What are the characteristics of classical and nonclassical 21-hydroxylase deficiency?
Classical form - neonatal infancy pregnancy
- simple virilising, salt wasting
Non-classical form - childhood/adult presentation
- premature baby, hirsutism, PCOS
What is the cause of androgen insensitivity syndrome?
What are the features of complete AIS?
- female external genetalia
- short, blind ending vagina
- no uterus, abdominal/inguinal testes
- absent prostate, axillary/pubic hair
- gynaecomastia - impressive breast development
How might someone with AIS present?
inguinal hernia (undescended testis!) primary amenorrhoea Elevated LH, Testosterone and E2 Oestrogen from aromatisation of Testosterone and LH driven gonad secretion T secretion 50% increased vs normal
What is 5alpha reductase deficiency?
Females but 46XY Unable to convert T to DHT Lack of virilisation Appear female Abdominal testes Primary amenorrhoea Virilisation at puberty Gender change in some cultures
How would a male with hypogonadism present?
- delayed puberty
- loss of libido, impotence
- gynaecomastia
- loss of body hair, reduced shaving frequency, thin skin
- decreased muscle mass, female fat distribution
- osteoporosis
- infertility +/- reduced testicular volume
What are used to measure testicular volume?
What is normal adult male?
Orchidometer
15-25ml
What are the causes of Primary hypogondism in males?
- trauma
- chemo
- undescended testes
- infections
- chromosomal abnormalities
- systemic diseases
What are the causes of secondary hypogonadism?
- pituitary tumours
- hyperPRL
- hypothalamic
- systemic disease
- obesity
- androgen use and abuse
How is hypogonadism investigated?
- clinical exam
- LH, FSH, testosterone
Further investigations to establish cause accordingly - liver function, prolactin, karyotype, imaging
What is Klineflelter’s syndrome?
47 XXY Primary hypogonadism - pea sized testes Feminisation - azoospermia, gynaecomastia Reduced secondary sexual hair Osteoporosis Eunuchs - tall stature Reduced IQ in 40% 20-fold increased risk of breast cancer
What are the clinical features of myotonic dystrophy?
Autosomal dominant Progressive muscular weakens Myotonia Mental retardation Frontal baldness Cataracts Primary gonadal failure
What are the clinical features of Kallman’s syndrome?
- Idiopathic hypogonadotrophic hypogonadism
- Anosmia in 75%
- Failure of migration of GnRH neurones
- X-linked autosomal recessive disorder
What are the safety issues with testosterone replacement?
behaviour
annual PSA, FBC, lipids, BP over 50yrs
What are the hazards of androgen abuse?
Psychological changes Prostate cancer Atrophy of testes Azoopermia Polycytheamia CV death
