Reproductive Axis Flashcards
The number of oocytes in the ovaries of a female fetes has reached a maximum by the end of the __1____
At birth ovaries contain 3M oocytes of which only 400,000 will remain by the time ____2_____ occurs
1) second trimester
2) puberty
Normal length of menstrual cycle?
28-35 days
Describe overview of the menstrual cycle?
1) Pulses of GnRH at about 2hr intervals stimulates FSH and LH release from anterior pituitary
2) LH stimulates ovarian androgen production by the ovarian theca cells
3) FSH stimulates growth of ovarian follicles and there is an associated rise in oestrogen which initially exerts negative feedback on hypothalamus causing decrease in FSH
4) Once oestrogen reaches a certain concentration it exerts positive feedback regulation resulting in an increase in FSH and LH surge
5) LH surge leads to ovulation (release of egg from dominant follicle) and regulates the formation of the corpus luteum. This secretes progesterone and oestradiol which decreases LH secretion by influencing GnRH pulsatility
6) Oestrogen initially and then progesterone cause uterine endometrial proliferation in preparation of possible implantation, if this does not occur the corpus luteum regresses and progesterone secretion and inhibit levels falls so the endometrium is shed (menstruation) allowing increased GnRH and FSH secretion.
7) If pregnancy HCG production from the trophoblast maintains corpus luteum function until 10-12 weeks of gestation by which time the placenta will be making sufficient oestrogen and progesterone to support itself.
What are the two phases and time lengths of the menstrual cycle?
Follicular phase (proliferative) - variable length Luteal phase (secretory)- constant length 14 days
What is the corpus luteum?
opened follicle that has closed off and secretes progesterone
How can timing of ovulation be predicted?
LH surge 34-36hrs before ovulation
What secretes progesterone?
The corpus luteum
Functions of oestrogen?
Increase thickness of vaginal wall, regulate LH surge, reduce vaginal pH through increase lactic acid production, decrease viscosity of cervical mucus to facilitate sperm penetration
Function of progesterone?
Pro-gestation: maintains thickness of endometrium responsible for infertile thick mucus (prevents sperm transport and helps prevent infection). Relaxes the myometrium (smooth muscle), functional progesterone withdrawal is thought to regulate birth.
Overview of hormones in male reproduction?
1) Pulses of GnRH are released from hypothalamus and stimulates FSH and LH from anterior pituitary.
2) LH stimulates testosterone production from Leydig cells of the testes
3) testosterone acts via nuclear androgen receptors to produce male secondary sexual characteristics anabolism and maintenance of libido. Testosterone inhibits GnRH secretion.
4) FSH stimulates the sertoli cells in the seminiferous tubules to produce mature sperm and inhibits which feedback to the pituitary to decrease FSH.
What cells produce testosterone in the testes? What stimulates this?
LH stimulates testosterone production from Leydig cells of the testes
What cells are stimulated by FSH to produce mature sperm?
Sertoli cells in the seminiferous tubules (within the testes)
What does LH and FSH do in males?
LH > stimulates testosterone production
FSH > stimulates formation of mature sperm
What are secondary sexual characteristics?
Features that appear during puberty in humans
What induces male secondary sexual characteristics? What are the characteristics?
Testosterone
Growth of pubic, axillary and facial hair, enlargement of external genitalia, deepening of the voice, sebum secretion, muscle growth and frontal balding
What induces female secondary sexual characteristics? What are the characteristics?
Oestrogens
Development of breasts, nipples, vaginal and vulval growth and pubic hair development. Also induce growth and maturation of the uterus and fallopian tubes.
What is puberty thought to result from?
Withdrawal of central inhibition of GnRH release
What is the definition of precocious puberty?
Development of secondary sexual characteristics earlier than normal, in girls before 8 and in boys before 9.
What effect does the corpus luteum have on hormones being secreted?
It secretes progesterone and there causes decrease in LH via negative feedback mechanisms
What is the follicle?
The follicle is a functional anatomical structure which forms part of the ovary and the egg is the cell that will mature in a microscopic part of inner wall of a follicle over spontaneous or stimulated ovarian cycle in normal conditions. Normally there is one egg in each fully grown follicle.
Definition of infertility?
Failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse in a couple who have never had a child
3 types of ovulatory disorders?
Type 1: Hypothalamic Pituitary Failure
Type 2: Hypothalamic Pituitary Dysfunction
Type 3: Ovarian Failure
(also hyperprolactinaemia)
Women with hypothalamic pituitary failure will have…
Low FSH and LH and not enough GnRH
Causes of hypothalamic pituitary failure infertility?
stress, excessive exercise, anorexia, low BMI, brain/ pituitary tumours, head trauma, Kallman syndrome (genetic disease isolated GnRH deficiency) and drugs (steroids and opiates).
Before giving medication for hypothalamic pituitary failure infertility what should you? (pre treatment)
Stabalise weight, stop smoking, reduce alcohol, 400 mg folic acid, check drugs, rubella immune, normal semen analysis and patent fallopian tube
What treatment can you give for hypothalamic pituitary failure infertility?
Pulsatile GnRH pump or FSH and LH daily injections. Both need US monitoring
Most hypothalamic pituitary dysfunction infertility is due to ….
Polycystic ovarian syndrome
Hormones in polycystic ovarian syndrome?
Normal GnRH, normal FSH, potential excess LH, normal oestrogen levels, ovary can’t read the hormones
What is polycystic ovarian syndrome characterised by?
Multiple small cysts within the ovary (which represent arrested follicular development) and an excess of androgen production from the ovaries
What is PCOS associated with?
Hyperinsulinaemia, insulin resistance, increased risk of T2DM, hypertension, hyperlipidaemia. and increased CVS risk
Diagnostic criteria for PCOS?
2 or more of
- Clinical and or biochem evidence of hyperandrogegism
- Oligo ovulation and or anovulation
- polycystic ovaries on US
Treatment of PCOS?
Weight loss to optimise, treat any acne and hirsutism (may give OC pill) treatment of fertility is by clomifene first line and is effective therapy if no results or surgery. Metformin may also improve ovulation due to association of PCOS with insulin resistance.
Risk of ovulation induction?
ovarian hyperstimulation, multiple pregnancy and ? over ovarian cancer
What type of ovulation disorders accounts for majority?
Hypothalamic pituitary dysfunction (PCOS)
Hormones in ovarian failure?
Raised LH and FSH but decreased oestrogen
Causes of ovarian failure?
Turner syndrome, other genetic syndromes, auto immune failure, surgery, radiotherapy, chemo, family history
Treatment of ovarian failure?
Need HRT- COCP
to have children egg or embryo donation needed or adoption and fostering
Overview of infertility treatment?
LIFESTYLE: stop smoking stop reduce drinking, caffeine in moderation, stop recreational drugs and methadone, healthy BMI (obesity reduces fertility in both men and women)
GENERAL: folic acid 400 micrograms before pregnancy and throughout 1st 12 weeks, MMR vaccine status, chlamydia screen
MANAGE FEMALE AND MALE FACTORS
IVF
What is the definition of male hypogonadism?
A clinical syndrome comprising of signs, symptoms and biochemical evidence of testosterone deficiency
Difference between primary and secondary male hypogonadism?
Primary: Problem with the tests themselves, spermatogenesis affected more than testosterone production
Secondary: Problem with hypothalamus and/or pituitary, the testes are capable of normal function but just aren’t being stimulated enough.
Hormones in primary vs secondary male hypogonadism? What are the other names therefore?
Primary: High LH and FSH (hypergonadotrophic hypogonadism)
Secondary: Low FSH and LH (hypogonadotrophic hypogonadism)
Both have low testosterone
What are causes of primary hypogonadism?
Acquired= any kind of trauma (torsion of testes, surgery radiation) infiltrative disease, medications (steroids and ketoconazole) Congenital= most common is klinefelters syndrome
Describe klinefelters syndrome and what causes it?
Caused by an extra X chromosome it is not inherited but due to disjunction.
Causes of secondary hypogonadism?
Acquired= any kind of pituitary damage (trauma, tumours), hyperprolactinaemia or medications (steroids, opioids) Congenital= Kallman's syndrome
Describe Kallman’s syndrome and what causes it?
Congenital cause of isolated GnRH deficiency caused by gene mutation, it is also associated with loss of smell (hyposmia/anosmia). Very rare condition.
Male has symptoms of hypogonadism and loss of smell think…
Kallmans syndrome
Pre pubertal onset of male hypogonadism presentation?
Small male sex organs
Decreased body hair, high pitched voice, low libido
Gynaecomastia
Eunuchoidal habitus
Post pubertal onset of male hypogonadism presentation?
Normal skeletal proportions- penis/ prostate size and voice
Decreased libido and spontaneous erections
Decreased pubic/ axillary hair, shaves less
Decreased testicular volume
Gynaecomastia
Decreased bone and muscle mass
Decreased energy
Management of male hypogonadism?
Testosterone replacement therapy
Transdermal gells, tablets, IM injections (short or long acting)
Important point about testosterone gel?
Interpersonal transfer so need to wash hands and site- can’t get someone else to apply it
5 Contraindications of testosterone therapy?
Confirmed hormone responsive cancer e.g. prostate or breast, possible prostate cancer, haematocrit more than 50%, severe sleep apnoea and HF.
What is haematocrit why does it need monitored in testosterone therapy?
Measures volume or percentage of RBC in blood
Testosterone increases it so if its already high then will get even higher and high score increases risk of stroke as the blood is more sticky.
Prolactin inhibits ______
GnRH
An ovarian follicle consists of ______1_______Theca cells produce ___2___ which are converted into ___3___ by granulosa cells
1) oocyte surrounded by granulosa and theca cells
2) androgens
3) oestrogens
What allows the menstrual cycle to begin again?
Progesterone decreases so FSH and LH are no longer inhibited
