Endo 9 - Causes of endocrine infertility Flashcards
What do Sertoli cells secrete that inhibits FSH and GnRH secretion from APG and Hypothalamus?
Inhibin
What are the 3 phases of the 28 day menstrual cycle
- Follicular phase - oestradiol and progesterone (-ve feedback present) secreted by ovaries, follicles in ovary growing
- Ovulation - big increase in Oestradiol, causing +ve feedback which causes big increase in LH (especially) and FSH secretion
- Luteal phase:
- If implantation doesn’t occur - endometrium is shed
- if implantation does occur - pregnancy
What is infertility
Inability to conceive after 1 year of regular unprotected sex
What is primary gonadal failure and what are the consequences of it
- Testes or ovaries dont work
2. Means that there are high levels of GnRH and LH/FSH, as no negative feedback from testosterone/oestradiol
Describe hypothalamic/pituitary disease?
Secondary gonadal failure
Problem with hypothalamus/pituitary so not enough LH/FSH secreted, and so low testosterone/oestradiol levels
What is hypogonadism (M)
What are the clinical features
Low functioning testes (in males)
- Loss of libido
- Impotence
- Small testes
- Decreased muscle bulk
- Osteoporosis
What are the 2 causes of male hypogonadism
- Hypothalamic-pituitary disease (secondary gonadal failure)
Can be caused by:
-Hypopituitarism
- Kallmans syndrome (improper development of GnRH neurones - causes anosmia and low GnRH).
- Illness/underweight (low leptin levels switch off GnRH neurones) - Primary Gonadal disease
Can be caused by:
- Congenital: Klinefelters syndrome (XXY)
- Acquired: Testicular torsion, chemotherapy - Hyperprolactinaemia
- Androgen receptor deficiency
Why might infertility be linked with an inability to smell (anosmia)
In hypothalamic-pituitary disease, Kallmans syndrome is a cause. This is an inability of the GnRH neurones to project fully. The GnRH neurones grow with the olfactory neurones, so sometimes the olfactory neurones are also not developed
What investigations should be done if male presents with hypogonadism
- LH/FSH/Testosterone - if all low, MRI pituitary
- Prolactin
- Sperm count - (azoospermia/oligospermia?)
- Chromsomal analysis (for Klinefelters)
What is the treatment for male hypogonadism
- Replacement testosterone for all patients
- If patient wants a child - and has Hypo/pit disease, can give LH/FSH
- If hyperprolactinaemia, can give dopamine agonist
Name 5 sites of endogenous androgen production
- Leydig cells (testes)
- Adrenal cortex - zona reticularis
- Ovaries
- Placenta
- Tumours
4 main actions of testosterone?
- Development of male genital tract
- Fertility in adulthood
- Controls secondary sexual characteristics
- Anabolic effects (muscle and bone)
98% of circulating Testosterone is PPB. The free plasma testosterone has 2 possibilities, which are
- Can be converted into DHT by 5a-reductase. DHT works via androgen receptor (AR)
- Can be converted into 17B-oestradiol (E2) via aromatase. E2 works via oestrogen receptor (ER).
Mechanism of action of DHT/E2 is via nuclear receptors
What are the clinical uses of testosterone
Test will increase:
- Lean body mass
- Muscle size and strength
- Bone formation and mass (in young men)
- Libido and potency
NB. Testosterone will not restore fertility - fertility requires treatment with gonadotrophin (FSH/LH) to restore normal spermatogenesis - i.e. if primary gonadal failure, having a child is dependent on how much term is left
Which 3 disorders in females may cause infertility
- Amenorrhoea
- Polycystic Ovarian Syndrome (PCOS)
- Hyperprolactinaemia
What are the 3 types of amenorrhoea (absence of periods)
- Primary amenorrhoea - failure to begin spontaneous menstruation by 16
- Secondary amenorrhoea - absence of menstruation for 3 months in a F who has previously had cycles (p much rules out congenital causes)
- Oligomenorrhoea - irregular long cycles
What are the causes of amenorrhoea?
- Pregnancy/lactation
- Ovarian failure - caused by:
- Premature ovarian failure (early menopause)
- Ovariectomy/chemotherapy
- Ovarian dysgenesis (Turners 45 X0) - Gonadotrophin failure (hypo/pit disease, Kallmans syndrome, low BMI (low leptin), post pill amenorrhoea)
- Hyperprolactinaemia (also switches off testosterone)
- Androgen excess, gonadal tumour
What investigations can be done for amenorrhoea
- Pregnancy test
- LH, FSH, Oestradiol
- Day 21 progesterone - it should be high, if low then they haven’t ovulated in that cycle
- Prolactin, thyroid function tests
- Androgens
- Chromosomal analysis (Turners 45 XO)
- Ultrasound scan ovaries/uterus
What is the treatment for amenorrhoea
- Treat cause (e.g. low weight)
- If primary ovarian failure - they are infertile - give HRT
- Hypothalamic/pituitary disease - give HRT for oestrogen replacement. If patient wants child, give gonadotrophins (LH + FSH), use as part of IVF treatment
What is the criteria to diagnose PCOS
2 of the following:
- Polycystic ovaries on uterus upon ultrasound scanning
- Oligo-anovulation
- Clinical/biochemical androgen excess
What are the clinical features of PCOS
- Hisutism
- Menstrual cycle disturbance
- Increased BMI
What is the treatment for PCOS?
- Metformin - improves insulin sensitivity
- Clomiphene (antioestrogenic) - it works by binding to oestrogen receptors in hypothalamus - blocks normal negative feedback - more GnRH and FSH/LH secretion
- Gonadotrophin therapy as part of IVF treatment
Prolactin secretion is regulated by?
Dopamine mainly (inhibitory effect) and TRH (thyrotrophin releasing hormone - stimulatory effect but small compared to DA)
What 2 effects does high prolactin have on the reproductive axis?
- Switches off GnRH pulsatility
2. Inhibits LH actions on ovary/testis
