Sex Hormones

Question 1

Define puberty

Answer 1

Stage where maturation of reproductive organs occurs and sex steroids such as oestradiol and testosterone are produced. Secondary sexual characteristics develop and ability to reproduce is attained.

Question 2

How does Tanner staging measure stage of puberty

Answer 2

Measures thelarche (breast development) in girls and increase in testicular volume in boys. Measures pubarche for both on a scale of 1-5. The Prader Orchidometer is used to measure testicular volume where above 15ml-25ml is considered adult size.

Question 3

What secondary sexual characteristics does oestradiol induce?

Answer 3

Breast development, Hair Growth (pubic then axillary), change to sweat gland composition (skin oiliness/acne) and changes to external genitalia.

Question 4

What secondary sexual characteristics does testosterone induce?

Answer 4

Deepening of voice, Hair Growth (pubic, axillary, facial), change to sweat gland composition (skin oiliness/acne) and changes to external genitalia.

Question 5

Describe sequence of pubertal events for girls

Answer 5

First sign is thelarche at 10.5 followed by onset of pubic hair at 11. Peak height velocity achieved at 11.4 with menarche at 12.8. Adult breast size reached by 14.6 and adult pubic hair present at 13.7.

Question 6

Describe sequence of pubertal events for boys

Answer 6

First sign is increase in testicular volume at 11.4. Onset of pubic hair at 12 followed by penile growth at 12.2. Peak height velocity reached at 14.1 with adult genital size achieved by 14.9 and adult pubic hair by 15.2.

Question 7

What is adrenarche and what does it cause?

Answer 7

Adrenarche is when the adrenal glands begin producing androgens resulting in pubarche.

Question 8

What is gonadarche?

Answer 8

Activation of HPG axis

Question 9

What is the GnRH secretion pattern?

Answer 9

Gonadotrophin releasing hormone is released in a pulsatile way through the day from the hypothalamus. Both sexes go through a minipuberty in the neonatal period where there is a spike in GnRH levels. In boys, this allows for testicular descent, penile length, Sertoli cell maturation and behavioural effects. There occurs a quiescence of the HPG axis through childhood until reactivated at puberty where there is an increased nocturnal pulsatile secretion of GnRH. Eventually, GnRH secretion becomes regular at adulthood.

Question 10

What is considered normal onset of puberty for girls and boys?

Answer 10

For girls, 8-13 years is considered normal age for onset of puberty. Below 8 considered precocious while beyond 14 considered delayed. Precocious onset of puberty more common in girls. For boys, a normal range is between 9 and 14 - delayed puberty more common in boys.

Question 11

When does menarche usually occur?

Answer 11

Roughly 2.3 years following thelarche and soon after peak height velocity is achieved. Mean age is 12.7 years but ranges from 10.7 to 16.1.

Question 12

What are the different kinds of amenorrhoea?

Answer 12

Primary amenorrhoea is where menstruation has not occured by 16 years of age. Secondary amenorrhoea is where menstruation has started but has not occured in 3-6 months.

Question 13

What is amenorrhoea and oligomenorrhoea?

Answer 13

Amenorrhoea is an absence of periods where no period has occured in 3-6 months or has less than 3 periods a year. Oligomenorrhoea is irregular or infrequent menstruation where cycles are longer than 35 days or range between 4-9 cycles a year.

Question 14

Describe follicular phase

Answer 14

1. FSH rises and 2-3 follicles start to grow.
2. The Graafian follicle produces E2 and Inhibin B is secreted by granulosa cells
3. These reduce FSH (by -ve feedback).
4. Restrict ‘FSH window’ and non-dominant follicles undergo atresia.
5. Hence, a dominant Graafian cell emerges and E2 continues to increase.
6. High E2 levels cause a positive feedback effect on pituitary and hence, LH levels surge causing ovulation.

Question 15

Describe luteal phase

Answer 15

Corpus luteum secretes progesterone and oestradiol

Question 16

Describe uterine cycle

Answer 16

Menstrual phase lasts 5-7 days followed by proliferative phase where oestradiol dominates. The endometrial lining regrows and new epithelial cells grow. Glands proliferate and there is an increase in stroma and arterioles. Progesterone dominates in the secretory phase. Here uterine lining transforms to be receptive to implantation. There is an increased volume of stromal cells creating thick spongy lining and cork-screw shaped glands secrete glycogen while spiral arteries coil and lengthen.

Question 17

What occurs once successful implantation happens?

Answer 17

If successful implanation occurs, embryo will produce b-Hcg which acts on LH receptors on the corpus luteum. This maintains production of oestrogen and progesterone in the first few weeks of pregnancy. If implantation doesn’t occur, corpus luteum dies off and progesterone levels reduce.

Question 18

How does GnRH pulsatility change during the menstrual cycle?

Answer 18

During follicular phase, pulses occur during every 90-120 mins but during luteal phase, pulses become less frequent occuring every 180-240 mins.

Question 19

What is primary hypogonadism

Answer 19

Hypogonadism is reduced oestrogen in females and reduced testosterone in males. This is primarily a problem of the gonads as characterised by high FSH and LH levels but low gonad hormones. In men, it is most commonly caused by injury to the testes, cancer of the testes or infection. In women, most common cause is menopause. The high FSH and LH is caused by the reduced negative feedback.

Question 20

What is secondary hypogonadism

Answer 20

Indicates a problem with the hypothalamus or pituitary gland where a low or normal amount of FSH and LH is produced. Low levels of testosterone and oestrogen. This is caused by a pituitary tumour or high prolactin. Prolactin inhibits release of GnRH.

Question 21

What happens to hormone levels during menopause?

Answer 21

Low E2, High FSH and LH, Low Inhibin

Question 22

What are the symptoms of menopause?

Answer 22

Skin dryness/hair thinning
Hot flushes/Sweating/Sleep Disturbance
Mood Disturbance
Osteoporosis - decreased bone mineral density as E2 stimulates osteoblasts
Sexual dysfunction - vaginal dryness, decreased libido
Weight gain
Amenorrhoea - peri within 1 year, post after
Cessation of fertility
Climacteric - irregular periods in years close to menopause

Question 23

What is treatment for menopause?

Answer 23

Oestrogen replacement - hormone replacement therapy. Oestrogen stimulates the endometrium.
Add progesterone if endometrium intact to prevent risk of endometrial hyperplasia/cancer.

Question 24

What is the role of anti-Mullerian hormone?

Answer 24

Acts as a marker of ovarian reserve by counteracting effects of FSH, preventing follicle recruitment so it can be preserved for ovulation later. Levels of AMH are a good indicator of resting pool. Peaks in adulthood and decreases from late 20s until very low before menopause. It is produced by granulosa cells in the ovaries.

Question 25

At what age does menopuase occur?

Answer 25

Between 45-55 with median age being 51. Only 1% of women experience menopause before 45.

Question 26

What is premature ovarian insufficiency?

Answer 26

Diagnosed by high FSH and up to 1/5 women with this can still conceive. Same symptoms as menopause. Can be caused by autoimmune conditions, genetic condition such as Fragile X syndrome or Turner’s syndrome, or cancer therapy (radiotherapy/chemotherapy)

Question 27

What are the forms of testosterone?

Answer 27

Testosterone is found in 3 forms: Bound to SHBG, weakly bound to albumin but can still dissociate and free testosterone. Only the latter is bioactive but only makes up 2% of plasma testosterone. 60% bound to SHBG and 38% bound to albumin.

Question 28

What causes late-onset hypogonadism in men?

Answer 28

Total plasma testosterone is unchanged through life but SHBG increases and free testosterone decreases so biological effects of testosterone decrease with age.

Question 29

How do testosterone levels vary?

Answer 29

Has a diurnal rhythm where it is highest in the morning, and hence causes early morning erections. Therefore must be measured before 11am. Also falls with glucose load.

Question 30

What are symptoms of testosterone deficiency?

Answer 30

Sexual dysfunction: Reduced libido, loss of early morning erections and erectile dysfunction
Reduced hair growth: ask about frequency of shaving
Lower energy levels: generally unwell or fatigued
Mood disturbance
Body composition: increased fat/reduced muscle mass
Gynaecomastia - breast enlargement in men
Problems with spermatogenesis: High levels of intratesticular testosterone needed.
Bone health needs checking: Testosterone converted to oestrogen

Question 31

How and where is testosterone converted to oestrogen?

Answer 31

Converted in Adipose tissue, Adrenal glands, Ovaries (Granulosa Cell), Testes (Sertoli Cells), Brain, Bone, Skin. Carried out by aromatase enzyme.

Question 32

What can influence the action of aromatase?

Answer 32

Age, Obesity, Insulin, Gonadotrophin levels, Alcohol, Aromatase inhibitors such as Anostrazole, Breast Cancer

Question 33

What are oestrone and 17B-oestradiol produced from?

Answer 33

Oestrone made from Androstenedione. 17B-oestradiol made from testosterone.

Question 34

How and where is dihydroxy-testosterone made?

Answer 34

Made in Testes (Seminal Vesicle, Epididymis), Prostate, Skin&raquo_space; Scalp, Liver. Reaction catalysed by 5-alpha-reductase. It is a more potent ligand for androgen receptors. Inhibited by 5-alpha Reductase Inhibitor such as Finasteride and prostate cancer.