LECTURE 29 - endocrine disorders affecting reproduction Flashcards
What are the 3 main ways in which endocrine disorders affecting reproduction can be acquired?
- congenital
- failure of full maturation at puberty
- acquired
May only be detected when there are problems conceiving
What is androgen insensitivity syndrome (XY)
- due to mutations in the androgen receptor (AR)
- occurs on a spectrum from partial –> complete
- affects 46 XY
- testis develop normally and secretes androgens
- insensitivity of fetus to androgens => Wolffian duct degenerates + female external genitalia formed - assigned female gender at birth
Presentation - inguinal hernia
- primary amenorrhoea (absence of periods)
What is 5α-reductase deficiency?
- affects 46XY
- unable to convert testosterone to DHT - required for male external genitalia
- appear female or have ambiguous genitalia
- primary amenorrhoea
- virilisation at puberty - male secondary sexual characteristics
- gender change
What is Kallmann syndrome?
- affects 1/10,000
- failure of migration of GnRH neurons, therefore cannot produce GnRH
- normally these neurones start off as precursors in olfactory placode, migrate to hypothalamus in development
- anosmia in 75% (no sense of smell)
What is precocious puberty?
- onset of secondary sexual characteristics before 8yrs (girls) or 9yrs (boys)
- F= 1/10,000
- M=1/50,000
- linked to short stature - premature fusion of epiphyses
Central causes
- sex hormones produced too early by HPG axis
- idiopathic - constitutional (no known cause)
- environmental endocrine disruptors
- obesity
Peripheral causes
- sex hormones produced by atypical means
- adrenal hyperplasia or tumour
What is delayed puberty?
- absence of SCC by 14yrs (girls) or 16yrs (boys)
- 95% constitutional - familial
- chemo/radiotherapy
- pituitary tumours
- Turner syndrome
- Kallmann syndrome
- AIS, 5α-reductase deficiency
How long is a normal menstrual cycle?
- 28 days is normal
- can be 26-32
- day 1 = first day of menses
What is amenorrhea?
- absence of menstrual cycle for more than 6 months
- primary amenorrhea - no menarche after 16yrs
- secondary amenorrhea = cased
Oligomenhorrhea = irregular cycles (less than 9 per year)
What are the presenting symptoms of endocrine disorders?
- oligomenhorrhea or amenorrhea
- infertility ~60% endocrine
- oestrogen deficiency
- hot flushes, poor libido, dyspareunia (painful intercourse)
- hyperandrogenism
- hirsutism, acne, androgenic alopecia
- galactorrhoea (breast milk without having baby)
What are the 3 main things that can go wrong with the HPG axis?
- Hypothalamic/pituitary disease - secondary/central causes
- Gonadal damage/failure - peripheral/primary causes
- Polycystic ovary syndrome
How are these endocrine disorders diagnosed?
- amenorrhea = pregnancy test (most likely issue)
- FSH/LH: test on day 2/3 - ovarian reserve, HPG disorders
- progesterone - day 21, test for ovulation
What is the progesterone withdrawal bleed test?
- aka progesterone challenge test
- used on amenorrheic women
- medroxyprogesterone acetate - 5 days
- bleed 2-7 days after completion of course
What are the primary causes of issues with the HPG axis?
- ovarian insensitivity/damage
- gonadotrophin secretion is normal
- high FSH/LH due to absence of feedback from oestrogen
What is premature ovarian failure?
- amenorrhea, low oestrogen, high FSH/LH - prior to age of 40 years
- affects 1% of women
Causes - often unknown
- congenital = Turner syndrome
- autoimmune
- latrogenic - chemotherapy and radiotherapy, surgery
What is Turner syndrome?
- XO - complete of mosaic
- affects ~1/2000
- normal oocyte growth requires both X chromosomes –> oocyte death
- normal ovary development requires normal germ cells –> ovarian dysgenesis
- can alleviate condition by giving growth hormone and oestrogen support
What effect does chemotherapy/radiotherapy have on fertility?
- variable depending on type/dose/duration of treatment
Preserving fertility - freezing embryos: need partner ~25% success rate
- freezing eggs: less successful ~10%
- requires time delay, ovarian stimulation
- freezing ovarian tissue: experimental. since 2004 ~100 babies
- donor eggs or adoption
What is ovarian reserve testing?
- test of how many eggs you have left/ how long you have in terms of fertility
- predicts response to ovarian stimulation in fertility treatment
- measure FSH/LH levels that rise as oestrogen falls
- can also measure Anti-Müllerian hormone (falls with age)
- can look at antral follicle count
What are the central causes of endocrine reproductive diseases?
- gonadotrophin secretion is low or absent due to problems with hypothalamus or pituitary
- low FSH/LH
- low oestrogen
What is hyperprolactinaemia?
- most common central cause
- increased prolactin from lactotroph cells of ant. pituitary
- suppresses release of FSH/LH
- will have oligo/amenorrhoea
- galactorrhoea
- can occur physiologically after having a baby: lactational amenorrhea
Common causes - prolactin secreting tumours
- tumours affecting pituitary stalk suppressing dopamine release (dopamine natural inhibitor of prolactin)
- drugs: dopamine antagonists (anti-psychotics)
Treat by surgery or with dopamine agonist
What are the lifestyle causes of Kallman syndrome?
- anorexia
- over-exercise
- stress
- -> all lead to low BMI/body fat/energy deficit –> decreased leptin, increased CRH = suppression of GnRH
- obesity: adipose tissue is oestrogenic, this will suppress HPG axis
What is polycystic ovarian syndrome (PCOS)?
- most common endocrine condition affecting 10% of all pre-menopausal women
Causes:
- oligo/amennorrhea (80%)
- hirsutism (30%)
- obesity (40%)
- infertility (30%) - anovulation
- polycystic ovaries on ultrasound
- increased risk of ovarian hyperstimulation syndrome
What is the Rotterdam Diagnostic Criteria for PCOS?
Women must have 2/3 of the following to be classed with PCOS
- oligo/amennorrhea
- clinical or biochemical signs of hyperandrogenaemia
- polycystic ovaries
What is dysmenorrhea?
- affects ~50-90% of women (10% severely)
Primary dysmenorrhea - higher levels of endometrial prostaglandins
- uterine hypercontractility
Secondary dysmenorrhea
- endometriosis (extra-ovarian endometrial growth)
What are the common presenting symptoms for male endocrine disorders affecting reproduction?
- loss of libido, reduced sexual behaviour, impotence
- infertility
- reduced testicular volume
- gynaecomastia
- loss of body hair, reduced shaving frequency
- decreased muscle mass, female fat distribution
How are male endocrine disorders affecting reproduction diagnosed?
- testosterone levels by age (decrease with age), testicular function
- FSH/LH - HPG axis
What are the primary causes of male endocrine disorders affecting reproduction diagnosed?
- testicular insensitivity/damage
- high FSH/LH due to absence of feedback from testosterone
What is Klinefelter syndrome?
- 47 XXY
- 1/500 males
- 2/3 of chromosomal abnormalities attending for infertility
- azoospermia (semen contains no sperm)
- firm pea sized testes - low testosterone + high FSH/LH
- many undetected cases
What are the central causes of male endocrine disorders affecting reproduction diagnosed?
- gonadotrophin secretion is low or absent due to problems with hypothalamus or pituitary
- low FSH/LH, low testosterone
How can male hypogonadism be treated?
- give exogenous testosterone
- sometimes can give aromatase inhibitors to recuse oestrogen
- can also give hCG: mimic for LH to stimulate testosterone
- weight loss
What are the risks of testosterone replacement and androgen abuse?
- psychological changes
- prostate cancer
- atrophy of testes
- azoospermia (infertility)
- polycythaemia
- cardiovascular: cardiac muscle hypertrophy, hypertension, arrhythmia
