Pubery, Menopause and osteoporosis

Question 1

Cause of puberty

Answer 1

Exact mechanism unknown -> thought that multiple factors lead to withdrawal of central GnRH inhibition –> this increases FSH then LH leading to an increase in testosterone/oestrogen levels

Question 2

Puberty in girls

Answer 2

Starts 9-13 and ends 12-18 –> Menarche occurs late (11-15) and growth starts and finishes earlier than boys
First sign is breast buds and USS can be used to assess ovarian and uterine development

Question 3

Puberty in boys

Answer 3

Starts 10-14, ends 15-17 –> full spermatogenesis occurs quite late in the process
Testicular volume >5mL indicates start of puberty
Rising serum testosterone is an earlier sign

Question 4

Definition of Precocious puberty

Answer 4

Development of secondary sexual characteristics (or menarche in girls) before the age of 9 is precocious
Can be idiopathic or secondary to a number of conditions

Question 5

Idiopathic (true) precocity of puberty

Answer 5

Rare in boys and commoner in girls –> diagnosed when other causes have been excluded –> can be normal and may run in families

Question 6

Treatment of Precocious puberty

Answer 6

Long acting GnRH analogues (given nasally, SC or implant) cause suppression by down-regulation of the receptor and are moderately effective
Cyproterone Acetate –>antiandrogen with progestational activity can also be used

Question 7

Causes of precocious puberty

Answer 7

Cerebral –> hypothalamic disease or tumours (always MRI to exclude, especially in boys)
Also: McCune-albright syndrome, Isolated premature thelarche, Isolated premature adrenarche

Question 8

Isolated premature adrenarche

Answer 8

Early development of pubic hair without any other changes –> usually after 5yrs and more commonly girls (particularly obese girls)
In boys the risk of androgen secreting testicular tumour should be investigated if androgens are high and LH is suppressed

Question 9

Isolated premature thelarche

Answer 9

Early, isolated breast development (age 2-4) – may regress or persist until puberty
No early follicular development

Question 10

McCune-albright syndrome

Answer 10

Usually girls

Presents with precocity, polyostotic fibrous dysplasia and skin pigmentation (cate-au-lait spots)

Question 11

Delayed puberty

Answer 11

95% of children with show some sign of puberty by 14yrs
Investigate at 15yrs –> mostly constitutional delay
Basal LH/FSH may indicate the site of defect and GnRH can indicate the stage of puberty reached

Question 12

Constitutional puberty delay

Answer 12

Very rare in women but occurs in boys –> May be family history and puberty, stature and bone age will all be in line

Question 13

Treatment of delayed puberty

Answer 13

If the delay is significant and this is causing problems then low dose, short term sex hormone therapy is used

Question 14

Menopause

Answer 14

Cessation of periods - 45-55yrs - FSH then LH rises over the 40s and oestogren drops causing cycle disruption
leading to scanty periods, amenorrhoea or menohagia
Uk average 50yrs 9mo

Question 15

Post-menopausal hormones

Answer 15

Grossly elevated LH (>50) and FSH (>25) with low estradiol

Raised FSH is the most reliable sign of being post-menopausal

Question 16

Premature menopause

Answer 16

Can occur from surgical removal of ovaries or radiation damage
Most commonly due to premature ovarian failure –> can be autoimmune or familial/genetic (occasionally linked to fragile X)
Must be diagnosed on repeat LH/FSH levels. Occurs in <1% women under 40

Question 17

Clinical features of the menopause

Answer 17

Most women will experience hot flushes (80%) –> can be disabling (20%). lasts average 4yrs, up to 12
Breast atrophy and vaginal dryness + non-specific loss of libido, self esteem, anxiety/depression/irritability, rashes & pains
Osteoporosis develops rapidly over 10yrs and increased risk of IHD

Question 18

Hormone Replacement Therapy (HRT)

Answer 18

Was widely used but increasing awareness of the risk has moved this to limited use if the symptoms are severe enough – not given universal to prevent osteoporosis –> selective oestrogen receptor modulators (SERMs) will likely be used in the future

Question 19

Risks of HRT

Answer 19

26% increased in risk of breast cancer but no risk in mortality (may be easier to treat) + Sig. increased risk of Uterine cancer
30% increased IHD and 40% increased stroke risk
Withdrawal bleeds unless the continuous oestogrens and progesterone is used

Question 20

Benefits of HRT

Answer 20

Symptomatic improvement – specific oestrogen deficiency symptoms respond very well and more general symptoms usually improve
Protection from osteoporosis but this is no longer sufficient indication for therapy
1/3 reduction in bowel cancer risk

Question 21

Treatment of premature ovarian failure

Answer 21

Almost always give HRT because the risk of oestrogen deficiency outweighs risk of HRT at the younger age

Question 22

Aging in males

Answer 22

There is a non-specific drop in sexual function and testicular volume decreases (SHBG and gonadotropin levels rise) – if premature hypogonadism occurs testosterone replacement should be used to protect from osteoporosis
Androgen inhibition is also used to combat prostatic hypertrophy

Question 23

Management options for hot flushes or night sweats

Answer 23

Lifestyle factors are first line, HRT is most effective. Tibolone is usable if more than 12months since last period, Clonidine use is often limited by side effects (dry mouth, dizziness & nausea)

Question 24

Oestrogen production in the body

Answer 24

The ovaries produce 17B-oestrodiol which is converted into estradiol. After the menopause the majority of the estrogen is produced by peripheral fat as estrone, before the menopause estrone is produced from androgens in the adrenal cortex (70%) and the ovaries (30%). Obese women have more.

Question 25

Causes of Menorrhagia and dysmenorrhoea in the peri-menopausal period

Answer 25

Lack of progesterone causes the endometrium to break down causing bleeding and pain

Question 26

Indications for HRT

Answer 26

Most commonly it is for control of vasomotor symptoms.
Can also be if menopause is premature but no longer given standardly to prevent osteoporosis. Give oestrogen plus progestogen if they have a uterus.

Question 27

Contra-indications for HRT

Answer 27

Pregnancy or breast feeding
Undiagnosed abnormal vaginal bleeding
Active or recent angina or MI
Suspected, current or past Breast, Endometrial or other oestrogen dependant Ca
Active liver disease with abnormal LFTs
Uncontrolled HTN

Question 28

Use of cyclic vs continuous HRT

Answer 28

Cyclic - If the last period was less than one year ago.

Continuous - if been on cyclic for 1yr OR >1yr since last period OR 2yrs since last period if menopause was premature