Reproductive System Week 3 Flashcards
Define the terms:
- Thelarche
- Pubarche
- Menarche
- Adrenarche
Thelarche - development of breast
Pubarche - development of axillary and pubic hair
Menarche - first menstrual period
Adrenarche - onset of an increase in the secretion of androgens
Define puberty
The series of events leading to sexual maturity
It is a time of accelerated growth, skeletal maturation, development of secondary sexual characteristics and achievement of fertility
Why has the age at which puberty occurs dropped significantly over the past 150 years?
Improved nutrition and living conditions
When are primary sexual characteristics established?
Before birth
What can the sequence of events in puberty be described as?
Age variable - between individuals and between different sexes
Order consistent
Describe briefly the events that occur in puberty
Accelerated somatic growth
Maturation of primary sexual characteristics (gonads and genitals)
Appearance of secondary sexual characteristics (pubic and axillary hair, female breast development, male voice change)
Menstruation and spermatogenesis begin - marks end of puberty
What triggers the start of puberty?
Maturation of the hypothalamic pituitary gonadal axis
Hypothalamic pulsatile release of GnRH
Increased pituitary gonadotropin in response to pulsatile GnRH is the endocrinologist hallmark of puberty (remember LH responds to pulsativity but FSH responds to intensity of GnRH)
If most parts of the reproductive system are able to work before the start of puberty, why dont they under normal circumstances?
Because hormone levels are too low due to low GnRH secretion
Why is the first ejaculation more difficult to date precisely than the first menarche?
Happens nocturnally
Do the menarche and the first ejaculation mean that the individual is fertile?
No, in early puberty the ovary does not ovulate and the ejaculate consists of small quantities of seminal plasma lacking spermatozoa
Just a sign that the gonads have awakened - beginning to assume adult levels of activity
Why do boys end up taller than girls on average?
Because they start their growth spurt later - they are taller when they start the growth spurt
What is the growth spurt?
An acceleration, followed by a deceleration of growth in most skeletal dimensions
The height gain between take off and cessation is similar in boys and girls and therefore the height difference is due mostly to the difference in height at take off rather than in height gained in the spurt
How many years later on average do boys start their growth spurt compared to girls?
2 years
What causes the growth spurt to end?
Closure of the epiphyseal growth plates
What effect does oestrogen have on the growth plates?
Causes them to close earlier in girls
What hormones does the growth spurt depend on?
Sex hormones –> androgens –> retention of minerals by body to support bone and muscle growth
Growth hormone –> secreted from pituitary –> increases TSH –> increases metabolic rate –> promotes tissue growth –> increased androgen release
What other changes occur in body composition during puberty?
Men get more lean mass (1.5 times women)
Women get twice as much body fat as men
Skeletal mass of men 1.5 times that of women
What is responsible for the greater average strength of men compared to women?
Greater number of larger muscle cells - anabolic effects of androgens
At what ages in women and men do the earliest changes in body composition at puberty occur?
6 - women (start getting more body fat)
9 - men (start getting more lean mass)
What secondary sexual characteristics are regulated by oestrogen?
Growth of breast and female genitalia
Maturation of internal reproductive organs
Growth of pelvis
Deposit of subcutaneous fat
What secondary sexual characteristics are regulated by androgens secreted from ovaries and adrenal gland?
Growth of female pubic and axillary hair
Bone growth
Increased secretion from sebaceous glands
Which secondary sexual characteristics are regulated by testicular and adrenal androgens?
Genitalia
Body hair
Deepened voice - enlarged larynx and laryngeal muscles
Growth of sex accessory structures (prostate)
What is the earliest detectable endocrine change associated with puberty?
Progressive increase in adrenal androgens - particularly DHEA and DHEAS (Adrenarche)
Between what ages does Adrenarche occur?
8-15 years
When does most gonadotropin secretion initially occur?
At night
What happens to levels of LH as an individual progresses through puberty?
Initially most secretion occurs at night
In late puberty - daytime pulses also increase but still less than those occurring at night
Until finally the adult pattern of higher basilar levels achieved - no pulsing variation throughout the day
How do testosterone levels change over puberty?
Follows LH in boys
Smaller increases in girls
How do oestrogen levels change over puberty?
In girls, rise consistently from low levels to the levels seen in mature women
Smaller rises in boys
What is thought to stimulate the increased GnRH release that occurs during puberty?
Neuropeptide transmitter Kisspeptin 1 from arcuate nuclei
Released in pulses that Mach the pulsatile secretion of GnRH
What are two hypotheses for the decreasing age of puberty?
Have to reach a critical weight:
- (47kg women and 55kg men) therefore improved nutrition, living conditions, healthcare has contributed
- leptins may be involved - secreted by white adipocytes - marker of fat content - rises during puberty - mutations in gene or receptor gene fail to enter puberty - treatment with leptin can overcome this - but unable to trigger precociously - maybe a background permissive signal essential for triggering signal to operate
- T3 and T4 may also have permissive role
- malnutrition associated with delayed menarche
- primary amenorrhoea common in lean female athletes
- body fat set point noticeable in girls with fluctuating body weight due to anorexia nervosa
Photoperiod:
- light:dark cycle known to affect reproduction in animals
- pineal gland - melatonin
- western world - electricity - prolonged daylight
- little evidence
- pineal tumours can affect puberty
What is the first detectable phenotypic change in puberty?
Breast enlargement
Testicular enlargement
When do levels of LH and FSH increase and what does this cause?
Between 9-12
Amplitude of pulse increases - especially at night
Initiates gonadal development
When does the LH and FSH increase occur in males?
~10
How is pubertal development classified?
Tanner standard :
Girls - breast, pubic hair, axillary hair, menarche
Boys - testicular volume, penis enlargement, pubic hair, axillary hair, spermarche
Monitoring of pubertal growth acceleration (2-3 times greater than prepubertal)
What age does puberty begin in girls?
9-13
What age does puberty begin in boys?
10-14
What is the growth velocity in boys and girls?
Boys- 10.3 cm/year
Girls - 9 cm/year
How long does puberty in last on average in boys and girls?
Boys - 3.2 +- 1.8
Girls - 2.4 +- 1.1
Describe the hormonal changes that initiate the first ovulation
LH surge indicates 1st ovarian cycle
Not sufficient to cause ovulation during 1st cycle
Brain and endocrine systems mature soon thereafter
Oestrogen in blood increases due to growing follicles
Describe precocious puberty
Occurring younger than 2 SD below the average age 1 in 5000- 1 in 10000 5-10 times more common in girls than boys Girls <8 Boys <9 Majority idiopathic May be due to: Gonadotropin dependent (central) Gonadotropin independent (neurological)
Describe the gonadotropin dependent causes of precocious puberty
Tumours: gliomas, astrocytomas, hamartomas, pineal tumours, HCG-secreting germ cell tumours (RARE)
CNS trauma or injury (infection, radiation, surgery)
Hamartoma hypothalamus
Congenital disorders - hydrocephalus, arachnoid cysts
Gonadotropin secreting tumours - (very rare)
Describe gonadotropin independent precocious puberty (pseudopuberty)
Secondary sexual characteristics develop due to increased production of male and female hormones Independently of HPG axis Gonad matures without GnRH stimulation Testosterone and oestrogen are elevated LH and FSH are suppressed
Describe the causes of gonadotropin independent precocious puberty
Congenital adrenal hyperplasia
Tumours:
HCG-secreting tumour - liver (not uncommon)
Choriocarcinoma gonads, pineal gland or mediastinum - ovarian tumours my cause masculinisation or feminisation - Leydig-cell tumours may cause early virilsation in males
Adrenal tumours - v rare
Testotoxicosis (familial male precocious puberty) - autosomal dominant - rapid physical growth, skeletal maturation and sexually aggressive behaviour in first 2-3 years of life
Exogenous oestrogen or androgen exposure (therapeutic or accidental)
What is delayed puberty?
Initial physical changes of puberty haven’t occurred by age 13 in girls or 14 in boys
or primary amenorrhoea 15.5-16 years (girls)
Pubertal development inappropriate
Interval between initial signs of puberty and menarche in girls/ completion of genital growth boys is > 5 years
What are the causes of delayed puberty?
Hypergonadotropic hypogonadism (impaired response of gonads to gonadotropins):
Turners syndrome
Post-malignancy- chemo/radiotherapy/surgery
Polyglandular autoimmune syndromes
Hypogonadotropic hypogonadism (impaired secretion of gonadotropins):
Congenital (+/- anosmia)
Hypothalamic/pituitary lesions (tumour, post-radiotherapy)
Rare gene mutation inactivating FSH/LH or their receptors
Describe Turner syndrome
Karyotype (45,X or 46,XX with X chromosome structural abnormalities)
Signs and symptoms:
- short stature (144-146cm)
- gonadal dysgenesis
- skeletal abnormalities
- cardiac and kidney malformation
- dysmorfic face
- no mental defect
- no impairment of cognitive function
Therapy - growth hormone/ sex hormone substitution
Cant correct the gonadal dysgenesis
What signals the end of reproductive life in females (generally)?
The menopause (climacteric)
What are the stages of menopause?
Pre-menopause
Menopause
Post-menopause
What are some general complaints of menopausal women?
Itchy, twitchy, sweaty, sleepy, bloated, moody and forgetful
Describe the premenopause
Typically age 40
Changes in menstrual cycle - shorter follicular phase
Ovulation early or absent:
-less follicles –> less oestrogen secreted –> less feedback to hypothalamus and pituitary –> more GnRH –> more LH and FSH
- FSH increases more due to lack of inhibin
Reduced feedback –> reduced fertility
Describe the menopause
Cessation of menstrual cycles (absent for 12 months - indicates start)
Age 49-50 but variable
No more follicles to develop
Oestrogen falls dramatically
FSH + LH rise dramatically- particularly FSH (inhibin gone)
What are the effects of the menopause ?
Vascular changes - hot flushes - ~80% - transient rises in skin temperature and flushing - not due to activity - often at night - relieved by oestrogen treatment
Lack of oestrogen causes:
- regression of endometrium, shrinkage of myometrium
- thinning of cervix
- vaginal rugae lost - thinner, drier
- involution of some breast tissue
- changes in skin
- changes in bladder - loss of pelvic tone - urinary incontinence - can be treated with oestrogen
Bone mass reduces by 2.5% per year for several years - increased osteoclastic activity - osteoporosis (greater risk in some compared to others - not just oestrogen) - increased risk of fracture - limited by oestrogen therapy - not first line therapy
Describe HRT
Relieves symptoms of the menopause Can improve well-being Oral or topical (gel or patch ) Gradually decrease oestrogen Can limit osteoporosis - no first line Not advised for cardio protection
Does reproductive life come to an end in males?
Not really Testosterone declines slowly Spermatogenesis still occurs No measurable physiological change Can still father children late in life (60s)
At what ages do Thelarche, Adrenarche, menarche and the growth spurt occur in girls?
Thelarche - 8-13
Adrenarche - 9-14
Growth spurt - 10-14
Menarche - 11-15
At what ages do testicular volume increase, penis length increase, pubic hair growth and the growth spurt happen in boys?
Testicular volume - 9.5-14
Penis length- 10-14
Pubic hair - 10-14
Growth spurt - 12-16
Why might precocious puberty be stimulated by meningitis?
Brain releases GnRH earlier
What are the effects of precocious puberty on bone growth? Would you expect the individual to be taller or shorter as a result?
Growth spurt starts earlier and therefore epiphyseal growth plate fuses earlier
Shorter final height
When does the growth spurt occur in relation to other events of puberty in boys?
Late
What treatments can be used for precocious puberty?
Central - idiopathic cause - GnRH agonist - negative feedback on hypothalamus –> reduce LH and FSH - continued until median age of puberty
- CNS lesions - surgery, chemotherapy, irradiation
Peripheral - Tumours - excision
- Iatrogenic - discontinue medication
What are the possible disadvantages of HRT?
Breast tenderness, leg cramps, bloating, nausea, headaches, depression, back ache, VTE, stroke, breast and endometrial cancer, gallbladderr disease
Why are oestrogen only preparations not given to women who have not had a hysterectomy?
Endometrial cancer risk
How are fibroids diagnosed?
Usually found incidentally during routine pelvic exam
Irregularities in shape of uterus
Ultrasound scan may be ordered if have symptoms - menorrhoea, pain, frequent urination, pain during sex
Hysteroscopy
Laparoscopy - outside womb
Biopsy may be taken
How would you assess if a woman’s menstrual blood loss is sufficiently great to have adverse effects?
Woman’s perception of what is normal for her
Count number of days of mesntruation
Count number and type of sanitary product used
Weighing sanitary products
FBC - anaemia
Menses cup
What options are there for treating heavy menstrual loss?
Under 35 -Iron supplements, NSAIDS, Tranexamic acid, oral contraceptive, oral progesterone, IUD (Mirena), dilation and curettage, uterine artery embolisation, ultrasound ablation, myomectomy,
Nearing menopause - Hysterectomy, endometrial ablation, endometrial resection
What advantages and disadvantages are there to removing ovaries as well as the uterus?
Disadvantages-
Will put into menopause - symptoms
Advantages-
Reduce the risk of ovarian cancer
Family history of breast or ovarian cancer
If gone through the menopause risk of ovarian cancer increases due to HRT - long exposure to oestrogen
Which hormone is responsible for proliferation of the endometrial lining of the uterus?
Estradiol
How large do follicles grow prior to ovulation?
Greater than 20mm avg diameter
How much estradiol is required for positive feedback on the anterior pituitary?
200 pg/ml for 50hrs
What happens during ovulation?
proteolytic enzymes and prostaglandins are activated, leading to the digestion of the follicle wall collagen
When is peak progesterone production noted?
1 week after ovulation
What causes menstruation?
Arteries coil together - blood supply to inner layer lost - endometrium dies and is sloughed off - no necrosis
What causes menstrual cramps?
Prostaglandin release
What is the main structure tethering the uterus ?
Uterine ligament
When is the menstrual cycle most regular? What are the effects of premenopause and menarche?
Between ages of 20-40
Longer just after menarche
Shorter in pre menopause
How much blood is lost in an average menstrual cycle?
37-43ml/cycle - usually max in first 48 hours
9-14% lose >80ml/cycle –>
60-70% of these are anaemic
What is the clinical term for heavy periods and what are the causes?
Menorrhagia Abnormal clotting Fibroids IUCD Cancer Progesterone contraception DUB (60%)
What are the types of fibroids?
Pedunculated - outside Intracavity (inside uterus) Submucosal Intramural Subserosal
What is DUB?
Heavy bleeding with no recognisable pelvic pathology, pregnancy or general bleeding disorders
What is the gold standard investigative technique for potential endometrial cancer?
Hysteroscope
Why is the a failure to identify endometrial cancer in the UK?
Male doctors reluctant to consider
Women who have been dismissed reluctant to come back - end up with metastases
Define amenorrhoea
Absence or cessation of a menstrual period in a woman of reproductive age
Pathological in 5% of women
Define primary amenorrhoea, the causes and treatments
Absence of menstruation by age 16 or absence of Thelarche or Pubarche by age 14
1-2% girls
Determine if uterus present or not, whether patent vaginal canal, whether breast development has occurred
Blood test (e.g. FSH) or karyotype
Causes:
Gonadal failure (35%) - streak gonads, absence of ovarian steroids, no breast development, internal and external genitalia normal - Turner syndrome (most common cause of primary amenorrhoea - >50% gonadal failure) - treatment - oral contraceptives - develop breasts and prevent osteoporosis - if Y chromosome present excise gonads to prevent 25% incidence of malignancy
Hypothalamic dysfunction (20-30%) - hypogonadotropic hypogonadism - CNS lesions (pituitary or hypothalamic tumours) may elevate prolactin - inadequate GnRH due to either insufficient synthesis or CNS neurotransmitter defect - treatment - oral contraceptive - brain imaging to rule out lesion
Vaginal agenesis and outflow tract obstruction (15-20%) - dysmenorrhea or pelvic pains suggest functional endometrium with obstruction to flow - absence of any symptoms despite normal secondary sexual characteristics suggests lack of endometrial tissue - vaginal agenesis (1-2.5/10000 female births) - congenital absence ofall or part of uterus and vagina - normal pubic differentiates from testicular feminisation syndrome - others are imperforate hymen (1/1000 women) and transverse vaginal septum (1/80000 women)
Testicular feminisation syndrome (10%) - androgen insensitivity - pseudohermaphrodite - testes, 46, XY genotype but female phenotype - X-linked recessive gene - absent or markedly diminished androgen receptors - treatment - testes should be left in place until after puberty completed - promotes breast development and growth
Define secondary amenorrhoea, the causes and treatments
Cessation of established menstruation - 3 months in a woman with a history of regular cycles or 6 months in a woman with a history of irregular periods
3-5% women (excluding pregnancy)
Causes:
Hypothalamic dysfunction (35%) - stress, weight loss, exercise, drugs - sustained decrease in GnRH pulse frequency and amplitude - treatment - behavioural modification or oral contraceptives - therapy may be unnecessary if underlying cause not threatening to health
Polycystic ovarian syndrome (30%) - heterogenous disorder of unexplained hyperandrogenic chronic anovulation - etiology unknown - treatment - oral contraceptive, progestins, insulin-sensitising agents, clomiphene citrate (First line treatment if desire pregnancy), ovarian drilling with laser
Pituitary disease (20%) - prolactin secreting pituitary adenoma most common lesion - iatrogenic hyperprolactinemic amenorrhoea caused by drugs should be excluded - Empty sell syndrome and Sheehan syndrome are rare - treatment - surgical resection for pituitary macroadenomas - other hyperprolactinemic patients followed with serial prolactin levels and head imaging to exclude macroadenoma development - therapy of empty sella and Sheehan syndromes involves hormone replacement
Asher man syndrome (5%) - intrauterine synechiae (adhesions) - interfere with normal endometrial growth and shedding - caused by vigourous uterine curettage in early pregnancy, pelvic TB in developing countries - treatment - hysteroscopic lysis and stimulation of endometrium with oestrogen
What is endometrial ablation ?
Burn the endometrium with laser in hopes of thinning the layer and therefore reducing cyclic blood loss
Good success rate
Sometimes needs repeating
What are the iatrogenic causes of irregular bleeding?
IUD
Oral/injectable steroids for contraception or hormone replacement
Tranquillisers and other psychotropic drugs
Oral contraceptives - irregular bleeding during first three months, if doses missed, vomit/diarrhoea, smoker, St. John’s wort, ginseng
Long-acting progesterone only contraceptives frequently cause irregular bleeding
What should be ruled out first when diagnosing abnormal vaginal bleeding?
Pregnancy - first priority
Think about patient age - are they prepubertal, menopausal etc.
Complete list of medications needed - rule out interference with mesntruation
What are the physical, psychological and social effects of menstrual disorders?
Physical – Tiredness, Anaemia, Pain
Psychological – Depression, Irritability, Mood Swings, Anxiety
Social – Impact on ability to socialise/ swim/ perform sports (despite what the Tampon adverts state!) - embarrassment of heavy periods (leaks)
