Reproductive Lifespan Flashcards
What are the primary and secondary sexual characteristics?
PRIMARY = internal & external genitalia, sex chromosomes
SECONDARY = pubic hair growth
- male = genital development, spermatogenesis
- female = breast development, menstruation
What are the different stages of female puberty?
8-13yrs
- THELARCHE = breast development (begins at ~9-13yrs and continues to ~12-18yrs)
- Prepubertal —> Breast bud —> Juvenile smooth contour —> Areola & papilla project —> Adult
- ~12 months between stages
- Tanner staging of breast develoment - ADRENARCHE = pubic hair growth along labia and up as a triangle (begins at ~9-14yrs and continues to ~12-16yrs)
- MENARCHE = onset of menstruation cycle (~11-15yrs)
- GROWTH SPURT = peak growth velocity at ~10-13yrs but completed earlier than males (shorter timespan)
- ended by fusion of epiphyses
What are the different stages of male puberty?
9-14yrs
- GONADARCHE = growth of external genitalia (onset of puberty —> 6yrs)
- Pre-adolescent —> Lengthening of penis —> Further growth in length/circumference —> Development of glans penis & darkening of scrotal skin —> Adult
note: increased testicle size due to FSH-induced increase in seminiferous tubules
2. ADRENARCHE = pubic hair growth from base of penis to medial thighs (shortly after gonadarche)
3. SPERMATOGENESIS
- GROWTH SPURT = peak growth velocity at ~12-17yrs, starts ~12 months after first signs of puberty, starts after females but lasts longer
- ends when epiphyses fuse
+ nocturnal emission/ejaculation
note: high intra-testicular levels of testosterone are needed for spermatogenesis
How is the timing of puberty controlled?
Prior to puberty:
- possibly due to increased sensitivity of the hypothalamus to negative feedback
- possibly the central mechanisms of the hypothalamus have not matured yet
note: hypothalamus does not produce GnRH and does not respond to stimuli which would normally increase GnRH in the post-pubertal adult
- oestrogen is unlikely to be the main cause of menarche, as the average age of menarche has reduced over time (1800s = 17yrs, 2010s = 13yrs)
How is the onset of puberty controlled?
Steady increase in GnRH secretion —> steady increase in FSH & LH
- menarche: increase in FSH —> follicular development —> beginning of menstrual cycle
- growth spurt: depends on GH & steroid hormones in both sexes, but testosterone is more potent than oestrogen (oestrogen closes epiphyses earlier in females)
- thelarche: stimulated by oestrogens
- adrenarche: stimulated by androgens in both sexes (source of androgens is from the adrenal gland in females)
- gonadarche (male): stimulated by testosterone
note: adrenal testosterone is different to testis-derived testosterone but stimulates the same processes
note: testosterone can be converted to oestrogen in some tissues (in significant amounts —> gynaecomastia)
Define precocious puberty, and give some examples of causes.
Development at an early age (before 8yrs) of the physical & physiological changes associated with puberty
- majority idiopathic
- neurological: early stimulation of central maturation e.g. pineal tumours (+++melatonin), meningitis (inflammation stimulates early rises in GnRH)
- true precocious puberty due to uncontrolled secretion of gonadotrophs/steroid hormone secretion e.g. hormone-secreting tumours, CNS lesions, post-encephalitis, neurofibromas, congenital adrenal hyperplasia, etc.
note: earlier fusion of epiphyses occurs —> reduced height as an adult
What defines the end of reproductive life in the male and female?
Male: no obvious event; spermatogenesis continues until ~60-70yrs
Female: menopuase/climacteric = when the ovaries cease to produce an ovum every 4wks, therefore menstruation ceases and the woman is no longer able to bear children
- PRE-MENOPAUSE (~40yrs)
- follicular phase shortens —> less oestrogen & inhibin secreted ———> reduced negative feedback —> increased LH & ++FSH (FSH affected by oestrogen & inhibin) —> reduced fertility —> ovulation can be early or absent - MENOPAUSE (~50yrs; variable)
- primordial follicles have been used up
- great decrease in oestrogen & inhibin —> increase in LH & +++FSH - POST-MENOPAUSE
Give some examples of effects of the menopause.
- “hot flushes” (~80%) = transient rises in skin temperature & flushing due to reduced oestrogen
- regression of endometrium & shrinkage of myometrium
- vaginal rugae lost
- involution of some breast tissue
- changes in skin (could be due to age) e.g. dryness, loss of collagen (wrinkles), thinning skin, hyperpigmentation
- changes in bladder (could be due to age) e.g. increase in freq., urgency, incontinence
- reduction in bone mass by ~2.5%/yr for several years due to loss of oestrogen —> osteoporosis
How can symptoms of the menopause be managed? What are the disadvantages of this treatment?
Hormone replacement therapy (oral/topical/gel) = combination of oestrogen +/- progesterone +/- progestin
Minimises symptoms of menopause, particularly osteoporosis
note: no longer advised for cardioprotection
Disadvantages:
- increased risk of breast/ovarian/uterine cancer due to constant proliferation of endometrial cells (hence oestrogen only preparations only given to women who have had a hysterectomy; progesterone inhibits this process)
- increased risk of stroke (therefore not recommended in previous stroke/DVT)
What is the average amount of blood lost per menstrual cycle? How can you assess whether menstrual blood loss is sufficient to cause adverse effects?
~ 30-45ml
NICE = heavy menstrual loss that interferes with a woman’s physical/social/emotional/quality of life
Menstrual loss greater than 80ml which will produce anaemia
Assess by pad and tampon counts & by measuring Hb/haemocrit levels
What is amenorrhoea? Give some examples of primary and secondary causes.
AMENORRHOEA = absence or stopping of menstrual periods
- PRIMARY: absence of menses by age 14yrs WITH absence of secondary sexual characteristics
- SECONDARY: established menstruation has ceased for 3 months in a woman with a history of regular cyclic bleeding and 9 months in a woman with a history of irregular bleeding
CAUSES: Most common causes of secondary amenorrhoea are pregnancy & menopause
Outflow tract obstruction:
- PRIMARY = uterine —> Müllerian agenesis (15% of cases)
= vaginal —> vaginal atresia, cryptomenorrhoea (severe cyclic abdominal pain in association with amenorrhoea), imperforate hymen
- SECONDARY = intrauterine adhesions e.g. Asherman’s syndrome - adhesions/fibrosis of endometrium e.g. due to dilatation & curretage of intrauterine cavity
Gonadal/end-organ disorders:
- PRIMARY = gonadal dysgenesis (most common cause is Turner’s syndrome), androgen insensitivity syndrome (testicular feminisation syndrome), receptor abnormalities for FSH/LH, specific forms of congenital adrenal hyperplasia
- SECONDARY = pregnancy (most common cause), anovulation, menopause (normal or premature), PCOS, drugs
Pituitary/hypothalamic/central regulatory disorders:
(inadequate FSH —> inadequate stimulation of ovaries
reduced oestrogen —> no endometrium stimulation)
- PRIMARY = Kallman syndrome - hypothalamic neurones responsible for GnRH secretion fail to migrate into the hypothalamus during embryonic development
- SECONDARY = hypo/hyperthyroidism, hypothalamic (exercise amenorrhoea, stress amenorrhoea, obesity, anorexia nervosa, bulimia), pituitary (haemochromatosis, hyperprolactinaemia, Sheehan syndrome - hypopituitarism due to ischaemic necrosis caused by blood loss & hypovolaemic shock during/after childbirth)
How should amenorrhoea be investigated and managed?
Investigations/history:
- menstrual history
- ?pregnancy
- ?contraception
- surgery
- medications
- stress
- diet
- chronic diseases
- weight change/BMI
- hair distribution
- thyroid function
- visual fields (pituitary disorders present as bilateral hemianopia)
- ?breast discharge
- ?abdominal masses/tenderness
- family history: age at menopause, thyroid dysfunction, diabetes, cancer
Management:
- rule out pregnancy
- levels of TSH, prolactin, FSH, LH (ovarian-axis)
- levels of testosterone (hirsutism)
- chronic disease: LFTs etc.
- CNS involvement: MRI
What is menorrhagia? Give some examples of causes.
Heavy vaginal bleeding not due to dysfunctional uterine bleeding (diagnosis of exclusion) = excessive (80ml+) & prolonged regularly (7days+)
Causes:
- most commonly due to distortion of the uterine cavity e.g. presence of fibroids (increases s.a. of endometrium) —> uterus unable to contract down on open venous sinuses in the zona basalis
- coagulation disorder
- endometrial carcinoma
- inflammation of endometrium e.g. intrauterine disease, PID
- pregnancy complications
How should menorrhagia be investigated and managed?
Investigations/history:
- FBCs for ?anaemia
- ?obesity
- ?androgen excess e.g. hirsutism, acne
- ?ecchymoses/purpura
- thyroid exam
- liver/spleen exam
- pelvic/uterine/cervical exam
Management:
- combined oral contraceptive pill
- progestrogens
- intra-uterine device
What is dysfunctional uterine bleeding? Give some examples of causes.
Abnormal bleeding with no obvious organic cause e.g. no pregnancy, pelvic disease, or systemic disease (therefore it is a diagnosis of exclusion)
Usually anovulatory
Changes in length of menstrual cycle due to disturbance to HPO axis: no progesterone withdrawal from an oestrogen-primed endometrium —> endometrium builds up and breaks down erratically
Causes:
- extremes in reproductive life
- PCOS
How should dysfunctional uterine bleeding be investigated and managed?
Investigations:
- hCG & TSH levels
- ?coagulation disorder
- ?cervical smear
- ?cancer (esp. if 35yrs+, with additional risk factors, tamoxifen use)
Management:
- IV/IM conjugated oestrogen therapy (for acute cases)
- progestrogen
- oral contraceptive pill
Define and contrast oligomenorrhoea, dysmenorrhoea, and pre-menstrual syndrome.
Oligomenorrhoea = uterine bleeding occurring at intervals between 35 days & 6 months (i.e. freq. periods)
Dysmenorrhoea = painful periods; cramping low abdominal pain radiating into the lower back/thighs
- PRIMARY = begin soon after menarche due to increased prostaglandin production by endometrium
- SECONDARY = caused by organic pelvic disease e.g. fibroids, endometriosis
Pre-menstrual syndrome = group of symptoms experienced by women of reproductive age in the week before menstruation
e.g. altered mental stability, fatigue, bloating, breast tenderness (mastalgia/mastodynia)
What is the definition of puberty?
Time of onset of sexual maturity, when reproductive organs become functional
How might the causes of primary amenorrhoea be distinguished by the levels of LH and FSH?
Normal plasma LH & FSH: ovary not responding, therefore no steroid hormones are produced OR tissues are not responding to steroid hormones
e. g. menstruation is occurring but products are not shed due to vaginal/cervical obstruction
e. g. androgen insensitivity syndrome = external female genitalia but no internal female ducts (as male gonad still produces MIH) (breasts & body hair normal)
Low plasma LH & FSH: pituitary/hypothalamus problem
e.g. pituitary tumour, anorexia nervosa, malnutrition, psychogenic causes
How can the stage of puberty be assessed?
Growth velocity on growth chart
Height & weight
Body hair pattern
Genitalia
Bone age (assess on X-ray; hand-wrist film most accurate)
How can you treat precocious puberty?
Treatment of underlying condition
Drugs to inhibit pituitary gonadotrophin secretion e.g. LRH analogues
or to block androgen action e.g. cryproterone
(but does not prevent epiphyseal closure)
Counselling
What is isosexual precocity? What is it caused by?
Precocious virilisation, but not more (precocious pseudopuberty)
Causes: increased testosterone
- congenital adrenal hyperplasia
- adrenocortical tumour
- 21-hydroxylase or 11-hydroxylase deficiency (glucocorticoids & mineralocorticoids are not produced, so all ACTH stimulates testosterone production)
What are fibroids? How are they diagnosed?
Benign tumours of smooth muscle (myometrium)
Mostly asymptomatic, but can cause abnormal bleeding (particularly menorrhagia) in women in their 40s
Tend to regress after the menopause
Investigations:
- transvaginal ultrasonography (will show mass but will not distinguish from other ovarian tumours)
- bimanual exam may allow palpation of large fibroids (irregularly shaped uterus)
- curretage/laparoscopy
- saline infusion sonography (sonohysterography)
What are the treatment options for women with heavy menstrual bleeding?
Under 35yrs:
- levonorgestrel-releasing intrauterine system for 12 months
- tranexamic acid/NSAIDs/combined oral contraceptive
- norethisterone daily from days 5-26 of cycle/injected for long-acting progestogens
Menopausal age:
- wait-and-see = serial exams & monitor blood loss
- GnRH agonist
- surgery = endoscopic resection/abdominal myomectomy/hysterectomy (hysterectomy only considered if other symptoms found, as the uterus will spontaneously shrink and may sort out the blood loss on its own)
What are the advantages and disadvantages of removing the ovaries during hysterectomies?
Advantages:
- potential reduced risk of ovarian cancer (although some can occur in the peritoneum de novo)
- potential reduced risk of breast cancer
Disadvantages:
- possible increased CVD risk due to early menopause
- sudden onset of menopause
- loss of ovarian androgen
Cochrane review = not enough RCTs to support removal or conservation of ovaries at time of hysterectomy in premenopausal women
What is the difference between primary and secondary ovarian failure?
Pre-menopause
- amenorrhoea
- low oestrogen
- high gonadotrophin
note: may have periods of intermittent fertility
PRIMARY = ovary fails to respond to normal stimulation from hypothalamus and pituitary
SECONDARY = hypothalamus and pituitary fail to provide gonadotrophic stimulation to the ovary
Is a woman fertile as soon as she begins menarche?
No - the first few menstrual cycles are anovulatory
