Repro Session 3 Flashcards
Disadvantages of HRT in post-menopausal women?
The use of estrogen therapy, without progesterone is associated with an increase in risk of uterine cancer (endometrial cancer, cancer of the lining of the uterus).
Treatment with progesterone along with estrogen substantially reduces the risk of uterine cancer (endometrial cancer) so that the risk of developing this cancer is equivalent to that of women not taking estrogen.
Users of oral hormone therapy (HT) (in the doses of the Women’s Health Initiative) for more than five years are at slightly increased risk of breast cancer risk, heart disease-MIs, and stroke than are nonusers.
Increased risk of DVT and PE- oestrogens increase clotting factors
abnornal vaginal bleeding
minor SEs- headaches, nausea, breast pain
why is oestrogen given along with progesterone in those PM women on HRT who haven’t had a hysterectomy?
Uterus still present, and oestrogen given alone increases risk of endometrial cancer
what happens to hormones during the menopause?
loss of follicular units decreases oestrogens and progesterone, which normally act by -ve feedback to inhibit the release of GnRH, FSH and LH, hence the decline causes an increase in gonadotropins, especially FSH (no inhibition by inhibin) over a period of yrs.
early changes in women during the menopause?
areas of skin hyperpigmentation (melasma), hot flashes., night sweats, reduced vaginal secretions and urogenital atrophy- particularly of vaginal epithelium and ovaries
later changes in women during menopause?
net decrease in bone mineral density and increase in cholesterol, increasing risk of OP and bone fractures
1st investigation for secondary amenorrhoea?
pregnancy (hCG test)
result of disruption to hypothalamic-pituitary-portal system?
high circulating levels of prolactin, low FSH and LH and ovarian atrophy
what is the fixed sequence of events occurring in girls at puberty, between 8 and 13 yrs of age?
breast bud (thelarche)
pubic hair growth (adrenarche)
growth spurt
onset of menstrual cycles (menarche)
stages of breast development in the female?
1: prepubertal, only papilla elevated
2: breast bud, breast and papilla elevated, areola diameter enlarged
3: juvenile contour, further enlargement of breast and areola
4: areola and papilla project above breast
5: mature stage, projection only of papilla
fixed sequence of events occurring in boys at puberty, between 9 and 14yrs?
genital development begins
pubic hair growth
spermatogenesis begins
growth spurt
stages of genital development in boys?
1: preadolescent, everything same size and proportion as in early childhood
2: scrotum and testes enlarged, growth in length of penis, texture of scrotal skin changed
3: penis grown primarily in length, and circumference
4: penis further enlarged, glans penis develops, darkening of scrotal skin
5: genitalia adult size and shape
stages of pubic hair development in male and female?
1: no pubic hair
2: sparse, pigmented, long, straight, mainly along labia and base of penis
3: dark, coarser, curlier
4: filling out towards adult distribution
5: adult in quantity and type, spreading to medial thighs in male
why are men generally taller than women?
growth spurt in boys is longer and slightly faster than in girls, and boys enter puberty later so have a longer period of pre-pubertal growth
how is growth spurt ended in both sexes?
fusion of epiphyses
what controls pubic and axillary hair growth in the female?
androgens released from adrenals- zona reticularis
what hormone is breast development during puberty dependent on?
oestrogens
why can some breast devlopment occur in males during puberty?
testosterone produced by leydig cells of testes can be converted to oestrogen in the tissues, and oestrogen stimulates breast development
problem for young girls with abnormally high oestrogen levels?
early puberty, with oestrogen closing the epiphyses earlier than normal, so girl may be very small as no further growth in length of bones can occur once epiphyses fused
what does the growth spurt depend on?
GH and steroids in both sexes
oestrogen closes epiphyses earlier in girls
what is the most important factor in the timing of puberty?
body weight
critical weight in girls for menarche?
47kg
how can body size be signalled to the hypothalamus?
via leptins- concentration related to amount of fat we have in body
* involved in appetite control- stimulate inhibitory neurone, and inhibit excitatory neurone to suppress appetite
rising leptin levels inhibit NPY, which then releases GnRH from its prepubertal inhibition
how is the body weight necessary for puberty to begin affected by how big we are gentically programmed to be?
those programmed to be smaller will have a lower body weight needed to be reached for puberty to begin
what structure in the middle of the brain detects the amount of light in our environement?
pineal gland
which hormone secretion is affected by the amount of light we are exposed to?
melatonin- secreted by pineal gland in dark
why might having more artificial light nowadays contribute to puberty occurring at an earlier age?
effect on secretion of melatonin from the pineal gland, which influences the hypothalamus and hence puberty onset
what name is given to puberty that occurs too early?
precocious: signs of puberty before age of 8
how can pineal tumours cause precocious puberty?
affect secretion of melatonin, giving impression that there is more light than there actually is
how can meningitis cause precocious puberty?
neurones prematurely activated due to inflammation
what ‘switches on’ puberty?
hypothalamus
How can hormone secreting tumours cause precocious puberty?
uncontrolled gonadotrophin e.g. LH,FSH or steroid e.g. testosterone, oestrogen secretion
overall effect of pre-menopause?
reduced fertility
what happens during the pre-menopause?
follicular phase shortens, ovulation occurs early or is absent- anovulatory cycles, which causes hormone sequences to not work properly. As follicles not developing as well, less oestrogen secreted so LH and FSH rise, FSH more, and there is reduced fertility
what is the menopause proper?
cessation of menstrual cycles
what produces the menopause?
ovary runs out of follicles
no more follicles left to develop, oestrogen falls dramatically, no inhibin, so FSH and LH rise, and ovary can’t respond to these
difference in blood levels of gonadotrophins before and after menopause?
before menopause- LH higher than FSH
after- FSH higher than LH as lose selective inhibition of FSH release by inhibin
what are hot flushes?
vascular changes result of oestrogen decrease, transient rises in skin temp and flushing
effects of menopause on oestrogen sensitive tissues?
uterus- endometrial regression, myometrial shrinkage cervix thinning vaginal rugae lost involution of some breast tissue changes in skin- thinning? changes in bladder- reduction in tone
why do children with increased body fat tend to not reach the full gentically predetermined adult height?
tend to start puberty earlier as higher leptin levels which feedback to hypothalamus to begin puberty, so they begin their growth spurt after a shorter period of prepubertal growth.
what is the start of puberty associated with?
steady rise in levels of FSH and LH
what might the rise in GnRH causing puberty onset be due to?
reduced sensitivity to low levels of circulating steroids that act be -ve feedback
more likely- maturation of central mechanisms
why does reproductive system not work before puberty?
hormone levels too low
advantages of HRT in post-menopausal women?
relief of symptoms
can limit osteoporosis, so reduce fracture risk
what is amenorrhoea?
absence of periods
primary amenorrhoea?
absense of menses by age of 14 with absence of SSC, or absence by age 16 with normal SSC
what is secondary amenorrhoea?
established menstruation ceased- for 3mnths in women with history of regular cyclic bleeding, or 9 mnths in woman with history of irregular periods. Usually happens to women aged 40-55.
what is oligomenorrhoea?
periods occurring at intervals of between 35 days and 6 mnths
what is menorrhagia?
heavy periods- excessive uterine bleeding (>80ml) or prolonged (>7 days) regular
what is dysmenorrhoea?
painful periods
what is premenstrual syndrome(PMS)?
various symptoms occurring in the 2 weeks before a woman’s period
most common cause of secondary amenorrhoea?
pregnancy
anorexia 1 of common causes
origins of amenorrhoea?
hypothalamic/pituitary
ovarian
outflow tract i.e. uterus, vagina, cervix
FSH levels if outflow tract obstructed, causing amenorrhoea?
normal, as hypothalamic-pituitary-ovarian axis is normal
what problems of outflow tract can cause primary amenorrhoea?
Mullerian agenesis- failure of uterus to develop
Vaginal atresia
Cryptomenorrhoea- hidden periods
Imperforate hymen- blood can’t leak out
what problems of outflow tract can cause secondary amenorrhoea?
intrauterine adhesions/scarring- Asherman’s syndrome, e.g. due to trauma or problems with childbirth
causes of primary amenorrhoea due to gonadal/end-organ disorder?
gonadal dysgenesis e.g. Turner syndrome- 45,X- 1 X chromosome, or 1 of X chromosomes defective, so would do genetic testing- karyotyping- short stature, cardiac abnormalities
androgen insensitivity syndrome- testicular feminisation syndrome, usually genetically male, but external genitalia look female
receptor abnormalities for FSH and LH
specific forms of congenital adrenal hyperplasia
causes of secondary amenorrhoea due to gonadal/end organ disorder?
pregnancy anovulation menopause premature menopause polycystic ovarian syndrome- hairy skin, skin problems, larger drug-induced
cause of primary amenorrhoea as result of pituitary and hypothalamic/central regulatory disorders
kallmann syndrome:the occurrence of hypothalamic gonadotrophin releasing hormone deficiency and deficient olfactory sense - hyposmia or anosmia. It is usually inherited as an X-linked or autosomal recessive disorder with greater penetrance in the male. However, new mutations may arise.
Gonadotrophin deficiency arises from a failure of embryonic migration of GnRH secreting neurons from their site of origin in the nose. The same defect affects the olfactory neurones resulting in olfactory bulb aplasia.
secondary amenorrhoea pituitary/hypothalamic disorders?
hypothalamus:exercise amenorrhoea, stress amenorrhoea, eating disorders and weight loss
pituitary: sheehan syndrome- hypopituitarism, hyperprolactinaemia- may have galactorrhea- spontaneous flow of milk from breast, prolactinoma can press on optic chiasm where optic nerve crosses causing bilateral hemianopia- visual dsiturbance, haemochromatosis
hypo or hyper thyroidism
evaluation of secondary amenorrhoea?
menstrual history contraception pregnancy surgeru medication weight change chronic disease, stress, diet
FH: age at menopause of mum, older sister, thyroid dysfunction, diabetes, cancer
physical examiniation: BMI hair distribution thyroid visual fields breast-discharge-prolactinoma? abdomen- masses? tenderness?
management of patient with amenorrhoea?
must always rule out pregnancy
ovarian-axis problem: investigate TSH, prolactin, FSH, LH
hirsuitism-excessive hair growth on women- testosterone, dehydroepiandrosterone (DHEAS), androstenedione, 17-OH progesterone
chronic disease- ESR, LFTs- liver metastases?
CNS-MRI- prolactinomas
what is dysfunctional uterine bleeding? (DUB)
excessively heavy, prolonged or frequent bleeding of uterine origin that is not due to pregnancy, pelvic or systemic disease
diagnosis of exclusion
anovulatory- most cases, so no corpus luteum forms, no progesterone produced, so oestrogen continuously produced with uterine bleeding
usually extremes of reproductive life and in parts with PCOS
may be erratic bleeding if ovulatory but progesterone secretion prolonged as oestrogen low
pathophysiology of DUB?
disorder of HPO axis, so changes in length of menstrual cycle
no withdrawal bleeding from an oestrogen-primed endometrium if progesterone given then stopped
endometrium builds up with erratic bleeding as it breaks down
causes of menorrhagia?
usually secondary to distortion of uterine cavity e.g. fibroids- benign growths (leiomyomas) of uterine wall which increase area which can bleed
uterus unable to contract down on open venous sinuses in zona basalis
usually ovulatory, so can get pregnant, and on a regualr basis
management of menorrhagia?
take history and FBC- can become anaemic very quickly
of structural of histological abnormality suspected, complete physical exam- anaemia, obesity, hirsuitism, acne, purpura, thyroid, galactorrhoea and ultrasound scan if abnormal
tment by GP with no exam if normal
NSAIDs e.g. tranexamic acid, or combined OCP
injected long-acting progestogens
diagnosis of DUB?
o HCG, TSH – Exclude pregnancy, thyroid
o Coagulation workup
o Smear if appropriate – Exclude cancer
o Sample endometrium
how are the 1st signs of puberty in the male brought about?
external genitalia development- testicle size increase due to FSH-induced increase in seminiferous tubules
what is true precocious puberty?
premature gonadotrophin secretion
most common symptom of fibroids?
abnormal bleeding, typically menorrhagia
potential disadvantage of removing ovaries as well as uterus in hysterectomy?
sudden onset of menopause as loss of ovarian sex steroids
general cause of heavy menstrual bleeding when regular cycles and timing of cycles?
thickening of endometrium over wide SA of uterus
what may cause inter-menstrual bleeding and post-coital bleeding in a woman?
cervical ectropion: columar epithelium of endocervix protrudes into the vagina, and subsequently bleeds as arteries of columnar epithelium are less resistant to damage than squamous epithelium of vagina
uterine cancer
