HPG axis & PCOS SP Flashcards
Anterior Pituitary - what does it produce?
TSH- thyroid GH FSH/LH ACTH Prolactin
Posterior Pituitary - releases?
Oxytocin: breast milk, stimulates contractions
ADH: BP
What inputs to the hypothalamus?
o Upper cortical inputs (thinking- brain)
o Heart rate, breathing, digestion (unthinking nervous system)
o Environment (light, temperature)
o Feedback from peripheral endocrine organs
- Also non-endocrine functions:
o Temperature regulation
o Activity of autonomic nervous system
o Control of appetite
Which neurons connect to the anterior pituitary?
Paraventricular neurons connect to medial eminence of hypothalamus -> veins -> anterior pituitary
Which neurons connect to the posterior pituitary?
o Supraventricular neurons connect to posterior pituitary (and produce ADH)
Explain the hypothalamic -pituitary -thyroid axis
Hypothalamus releases TRH -> anterior pituitary releases TSH -> thyroid releases T3/4
= THERMOGENESIS AND PROTEIN SYNTHESIS
Explain the hypothalamic -pituitary -adrenal axis
Hypothalamus releases CRH -> Anterior pituitary releases ACTH-> Adrenals release CORTISOL
= CELL HOMEOSTASIS AND FUNCTION
Explain the hypothalamic -pituitary -gonadal axis
hypothalamus releases GnRH -> anterior pituitary releases LH and FSH-> ovaries release oestrodial and progesterone
= OVULATION or
-> testes release testosterone and inhibin = SPERMATOGENESIS
Explain the hypothalamic -pituitary -growth hormone axis
Hypothalamus releases GHRH => pituitary, releases GH => Liver releases insulin like growth factor 1 and chondrosites
= LINEAR AND ORGAN GROWTH
LH and FSH
LH surge and FSH (smaller rise) stimulate ovulation.
The average adult menstrual cycle lasts 28-35 days, with approx. 14 to 21 days in the follicular phase and 14 days in the luteal phase.
There is little cycle variability ages 20-40 years.
Menstrual Cycle generally
Significantly more cycle variability for the first 5 to 7 years after menarche and for the last 10 years before cessation of menses. Women in their forties have slightly shorter cycles. Primarily due to changes in the follicular phase, in comparison, the luteal phase remains relatively constant
The Pill
The most important mechanism for providing contraception is the oestrogen induced inhibition of the midcycle surge of gonadotropin secretion- so that ovulation does not occur. Suppression of gonadotropin LH, FSH secretion during the follicular phase of the cycle, thereby preventing follicular maturation.
Cycles on the pill: not a regular menstrual cycle- withdrawal bleeds occur (hopefully) at regular intervals- sugar pills.
LH and FSH in men- actions on the TESTES
LH interacts with receptors on the leydig cell membrane to stimulate adenyl cyclase -> release of cAMP, through a series of incompletely understood intermediate steps enhances testosterone synthesis.
FSH interacts with receptors on the basal aspect of the sertoli cell membrane- regulates spermatogenesis
What is hypogonadism?
There are two types- primary and secondary.
what are the causes of each?
reduction or absence of hormone secretion or other physiological activity of the gonads (testes or ovaries).
Can be primary (ovaries, testes) or
secondary (pituitary- “hypogonadotropic hypogonadism”)
Common Clinical Signs of Primary Hypogonadism in
- Women
- Men
Women:
- Menopause (hot flushes, depression cognitive symptoms, vaginal dryness, sleep disturbance)
- “hot flushes” are thought to be due to thermoregulatory dysfunction initiated at the level of the hypothalamus by oestrogen withdrawal.
o FSH and LH rise at menopause
- Early menopause: by definition <age 40 (but usual age of menopause around 50 years)
- Chemotherapy – alkylating agents
- Pelvic irradiation
- Turners syndrome- often primary amenorrhea
- Mumps, CMV
- Autoimmune disorder
Men
- Gynecomastia
- Infertility
- Low testeosterone , loss of bone density +++
What are the clinical symptoms of Secondary Hypogonadism in Women
LH and FSH do not rise appropriately in setting of low estrodial levels.
Women:
- Symptoms amenorrhoea, oligomenorrhoea
- Loss of ovulatory cycles
- Hot flushes not a feature
- Loss of bone density +++
- Common causes: anorexia nervousa, abnormal weight loss, abnormal weight gain, severe physical or physiological stress
What are the clinical symptoms of Secondary Hypogonadism in MEN
Men:
- Reduced libido, depressed mood
- Decreased muscle mass and body hair
o But do not occur for a year or many years
- Hot flushes only occur when the degree of hypogonadism is severe
- Change ratio of muscle mass: fat mass
- Gynaecomastia more likely to occur in primary than secondary hypogonadism
Other causes of Secondary Hypogonadism
Other causes of Secondary Hypogonadism
• Type 2 Diabetes (men) – a hidden epidemic
o Check testosterone, LH, FSH
- Haemachromatosis- pituitary, testes (less common)
- GnRH agonists can cause a surge in LH and FSH but then cause a receptor down regulation and the end result is hypogonadism. Eg. Goserelin used for treatment of prostate cancer
- Pituitary tumours
o Suppressing LH, FSH: mass effect
o Pituitary tumour secreting prolactin will suppress GnRH secretion and subsequently suppress LH and FSH
• 10-20% cases amenorrhea may be due to high prolactin!!
Define
Oligomenorrhea
Amenorrhea
Primary Amenorrhea
Oligomenorrhea: infrequent menstruation >6 weeks
Amenorrhea: >3 months without menstruation (look for secondary causes)
Primary Amenorrhea: failure to menstruate by a given age (around 15)
What are some causes of secondary amenorrhea
• Exclude pregnancy • OCP can cause amenorrhea in some women • Disorders of energy expenditure: - Anorexia nervosa - Strenuous exercise - Low BMI of any cause –eg. Coeliacs disease, malabsorption due to inflammatory bowel disease • Hyperandrogenism-Adrenal disease • Hyperprolactinaemia - Lactation -Drugs - Prolactinoma - Hypothyroidism - Hyperthyroidism, hypothyroidism (severe) • *MUST distinguish from PCOS
When a woman presents with amenorrhea, what are some clinical questions to ask?
- Duration
- Did you have regular cycles that then ceased or became irregular
- Is the OCP complicating this history?
What is PCOS?
- Not a disease
- 5-10% of women
- Conterstone = insulin resistance (and higher LH levels)
- Irregular menstrual cycles, hirsutism, obesity, classic ovarian morphology (occasionally there is a pattern of secondary amenorrhea)
What are the criteria for PCOS?
Criterion
- Menstrual irregularity due to oligo or anovulation
- Evidence of hyperandrogenism whether clinical (hirsutism, male pattern balding or acne) or biochemical (high testosterone)
- Exclusion of other causes of hyperandrogenism and menstrual irregularity
- Non classic congenital adrenal hyperplasia (check 17-OH progesterone)
- Androgen secreting tumours (DHEAS)
- Hyperprolactinaemia (prolactin)
- Cushing’s syndrome (24 hour urinary free cortisol)
- By definition it is a diagnosis of exclusion
What would be the clinical presentation for PCOS?
• Difficulty conceiving
• Obesity
• Hirsutism
• Menstrual disturbance of PCOS (classically has a pubertal onset)
o Irregular periods
o Risk of very heavy menstrual bleeding
• Other features: insulin resistance, type 2 diabetes, obesity, dyslipidemia, NAFLD, metabolic syndrome, higher rates of sleep apnoea, mood disorders?
