1a Sex Hormones Flashcards
What are the four hallmarks of puberty?
- Development of secondary Sexual Characteristics
- Maturation of Reproduction Organs
- Obtaining ability to reproduce
- Production of sex-steroid hormones
What are the two main sex steroid hormone?
Oestradiol and Testosterone
What is meant by thelarche?
The onset of breast development
When is meant by menarche?
The onset of menstruation
What is meant by Pubarche?
The onset of pubic hair development
what scale is used to meant Breast development in femals?
tanner scale
What is gonadarche?
The onset of the activation of the gonads by the HPG axis
What is meant by spermarche?
The onset of spermatogenesis
When does adrenarche occur?
Starts around 2 years before gonadarche
What is adrenarche?
onset of adrenal androgen production
What is the first sign of puberty in males?
Increases in testicular volume
What is the first sign of puberty in women?
Thelarche
What is often used to see what the testicular volume should be at each stage of life?
Prader- Orchidometer
What hormone leads to the development of secondary sexual characteristics in females?
Oestradiol
What are the secondary sexual characteristics in females?
Breast Development
Hair growth (pubic and axillary)
Changes to sweat gland composition (skin becomes more oily and acne develops)
Changes to external genitalia
What hormone results in the development of secondary sexual characteristics in males?
testosterone
What are the secondary sexual characteristics of boys?
Increase in testicular volume
Pubic then Facial and Axillary hair development
Voice deepening
At what age does adrenarche occur in females?
6-9 Years Old
At what age does adrenarche occur in men?
7-10 years
What is the late sign of puberty in girls?
Menarche
At what age does puberty typically occur at in females and males?
Females - 8-13 Years
Male - 9-14 Years
What is an adult testicular volume?
> 15mLs
What is the average early pre-pubertal testicular volume?
Less than 4mLs
What are the adrenal androgens?
DHEA
DHEAs
Testosterone
How do the levels of FSH and LH change as girls and boys progress through the Tanner stages of development?
The serum levels of FSH and LH Increase
What is GnRH?
Gonadotrophin Releasing Hormone
What term is used to describe th secretion of GnRH?
Pulsatile - comes in waves
Why must GnRH secretion be pulsatile?
The continuous pulsatile administration of GnRH causes decreased LH/FSH secretion
What changes occur during mini-puberty?
Testicular descent out the stomach
Penile length increases
Sertoli cell maturation
When does the HPG axis undergo quiescence?
During childhood, before the onset of puberty
During puberty, what happens to the GnRH pulsatility?
There is increased nocturnal GnRH pulsatility
Describe how the HPG axis works?
Kisspeptin neurones associated with the hypothalamus regulate the pulsatile secretion of GnRH from parvocellular hypothalamic neurones into the primary capillary plexus within median eminence → Entering into the portal-hypophyseal pituitary circulation
GnRH stimulates the release of LH and FSH from gonadotrophs within the HPG. These hormones stimulate the ovaries and testes
What hormone is needed to maintain the corpus luteum?
hCG - human chorionic gonadotrophin
How does hCG provide support for pregnancy?
hCG maintains progesterone levels, which acts to maintain the endometrium lining, providing support for pregnancy
How many years after thelarche does menarche occur
2.3 years
What is meany by precocious puberty?
Early puberty (<8 years)
What i meant by primary amenhorrhoea?
When you never had a period before
What is meant by secondary amenorrhoea?
When you start menses but stop for 3-6 months
What is the most common cause of secondary amenorrhea in women?
Pregnancy`
Is precocious puberty more common in males or females?
Females
What is meant by delayed puberty?
When puberty starts after 14 years of age
Is delayed puberty more common in males of females?
Males
What is oligo-menorrhoea?
Irregular or infrequent periods >35 day cycle OR 4-9 cycles in total per year.
What is used as evidence of ovulation?
Mid-luteal D21 Progesterone
What happens in pregnancy that is different to a normal Menstrual cycle?
Beta hCG secretion → Activates FSH and LH receptors → Continues to support the corpus luteum → Secretion of progesterone
Outline the Menstrual cycle
- FSH rises
- 2-3 follicle are stimulated
- Makes E2 (oestradiol) and inhibin B
- These reduce FSH
- Therefore, those follicles which are highly FSH dependant die, and the dominant grafian follicle which is less reliant on FSH emerges
- E2 levels continue to rise, which causes a switch from negative feedback to positive feedback, leading to an LH surge
- Causes ovulation - egg released from follicle
What causes the swap from negative feedback to positive feedback during the follicular phase of the menstrual cycle?
High Oestradiol levels (E2) - causes a surge in LH levels
How does the corpus luteum form?
the remainder of the follicle after ovulation has occured forms the corpus luteum
What hormone is needed for the development of the Corpus Luteum?
LH
What hormone does the Corpus Luteum secrete?
Progesterone
if implantation does not occur, how does the corpus luteum degrade?
absent HCG stimulation → Shedding of endometrium lining → Menstrual cycle restarts
What is meant by atresia?
When the FSH dependant follicles die
Why is it essential thet GnRH is pulsatile?
Otherwise the receptors would become less sensitive
Why is the pulatility of GnRH higher during the follicular phase of pregnancy, compared with the luteal phase?
Progesterone which is secreted during the luteal phase negatively inhibits GnRH
What can be used as a surrogate marker for GnRH levels?
Serum LH
Why can GnRH levels not be measured directly?
GnRH is only released into local circulation; the hypo-physeal portal system
What is primary hypogonadism?
When you have low E2/Testosterone due to a problem with the hormone-secreting gland eg testes of ovaries
What is secondary hypogonadism?
When you have low E2/testosterone due to a problem with the hypothalamus or pituitary gland
What is secondary hypogonadism sometimes referred to as?
Hypogonadotrophic Hypogonadism
What happens to LH and FSH levels during primary hypogonadism?
They are high due to no negative feedback as the ovaries and testes are not producing E2/testosterone
what can cause primary hypogonadism in females and males?
Infection, trauma and cancer of the testes
What is the most common cause of primary hypogonadism in women?
Menopause - ovaries stop producging E2/inhibin, meaning FSH is higher
A rise in which hormone can cause secondary hypogonadism?
Prolactin
What happens to FSH/L levels during secondary hypogonadism?
They are normal / low
What does LH stimulate the secretion of?
Sex steroids
What are the symptoms of Menopause
Skin dryness/Hair thinning
Hot flushes/Sweating/sleep disturbance
Mood disturbance
Osteoporosis
Sexual dysfunction
Weight gain
Amenorrhoea
Cessation of fertility
Climacteric - Irregular periods in years close to Menopause
What is menopause hormone therapy?
When oestrogen is given to the patient to stimulate the endometrium to grow
What is added to the treatment of menopause if the endometrium is still intact?
Progesterone - prevents the risk of endometrial hyperplasia (increased thickness) or cancer
Why does menopause result in osteoporosis?
Decreased bone mineral density as E2 stimulates osteoblasts
When is gametogenesis initiated in males?
Puberty (gonadarche) → spermatogonia undergo differentiation and self-renewal
How many mature sperm are produced per second?
1500
Outline the lifespan of the an oocyte from before birth till puberty
Multiplication of Oogonia to ~ 6 million/ovary which form primary oocytes in the ovarian (primordial) follicles → Halted in prophase I
Proportion of primordial follicles undergo atresia → 2 million/ovary → 0.5 million/ovary at puberty
Which cells secrete anti-mullerian hormone?
Granulosa cells in the ovaries
What is AMH?
Anti-Mullerian Hormone
What is AMH used for?
An Ovarian reserve marker - shows you how many eggs a patient may have left
What is meant by premature ovarian insufficiency?
Early menopause
how do you diagnose Premature Ovarian Insuffieicny?
High FSH levels - two tests, done at least 4 weeks apart
What happens to AMH levels at menopause?
The are very low
What are the causes of Premature Ovarian Insufficiency?
Autoimmune causes eg Graves Disease
Genetic Influences
Cancer Therapy - radiotherapy / cancer treatment in the past
What is the “male menopause” sometimes called?
Andropause
What occurs in andropause?
Decrease in sexual satisfaction or a decline in a feeling of general wellbeing with low levels of testosterone in older men
Roughly how much testosterone is ‘free’?
2% of testosterone
What is most of the testosterone bound to?
Sex-Hormone Binding Globin (SHBG)
Why is some testosterone still bioavailable?
38% is bound to Albumin weakly
Why is there a male menopause?
Total testosterone is unchanged by SHBG is increased, meaning there is less “free” / bioavailable testosterone
Why do morning erections occur?
testosterone release is diurnal, meaning it is higher in the morning and decreases thorughout the day
What can reduce testosterone levels?
Glucose
Why must testosterone be measured before 11am and when the patient is fasting?
Glucose levels can reduce testosterone levels
What are the symptoms of testosterone deficiency?
Sexual dysfunction - Reduced libido
Erectile dysfunctions > Loss of early morning erections
Hair growth - Frequency of shaving?
Energy levels - General wellbeing, Fatigue
Mood disturbance
Body composition changes - Increased fat + reduced muscle mass
Gynaecomastia (breast enlargement in men)
Spermatogenesis - High levels of intertesticular testosterone needed
Bone health - Testosterone sometimes converted to oestrogen when present; lack thereof can lead to osteoporosis
What enzyme converts testosterone to oestrogen?
Aromatase enzyme
Where can aromatase enzyme be found?
Adipose
Adrenal Glands
Ovaries (Granulosa)
testes (Sertoli)
Brain
Bone
Skin
What does aromatase convert Androstenedione into?
Oestrone
What does aromatase convert Testosterone into?
17B-Oestradiol
What factors cause increased activity of aromatase?
Age
Obesity
Insulin
Gonadotrophins
Alcohol
What inhibits aromatase?
Breast Cancer
Tamoxifen
What can aromatase inhibitors such as anostrazole be used to treat?
Breast Cancer
Where can you find the enzyme 5-alpha-reductase?
Testes (seminal vesicle, epididymis)
Prostate
Skin > Scalp
Liver
What does 5-alpha-reductase do
Converts Testosterone into Di-Hydro-Testosterone
What is the difference between testosterone and dihydrotestosterone (DHT)?
Dihydrotestosterone is a more potent ligand for the androgen receptor
What does DHT have a role in?
DHT has a role in pubic and facial hair growth, prostate and male pattern baldness
What can 5-alpha-reductase inhibitors such as finasteride be used to treat?
Prostate cancer
What inhibits 5-alpha-reductase?
Finasteride
