Menstrual Cycle
Follicular (preovulatory) Phase
- At the beginning o the menstrual cycle the ovarian follicles are underdeveloped and plasma oestradiol concentrations are low
- Levels of FSH and LH rise as a consequence of diminished negative feedback by oestrogen
- LH and FSH cause a cohort of follicles to mature but by day 7 one follicle becomes particularly sensitive to FSH and matures whilst the rest atrophy
- LH stimulates oestradiol secretion, the concentration of which rises steadily. This stimulates the regeneration of the endometrium
Ovulation
- The rise in plasma oestradiol triggers a surge of LH by positive feedback. Ovulation occurs 16hr later
Luteal (post ovulatory of secretory) Phase
- After ovulation the high levels of LH stimulate the granulosa cells of the ruptured follicle to form the corpus luteum which secretes progesterone and oestradiol
- Progesterone prepare the endometrium for implantation of the ovum
- If the ovum is not ferilised, levels of oestrogen and progesterone fall, the endometrium sloughs off and menstrual bleeding occurs
- As the plasma ovarian hormone levels fall, FSH and LH levels can rise again and the cycle recommences
- Progesterone is associated with a rise in body temperature which may be monitored to determine the time of ovulation
Menopause
- Defined as the time of permanent cessation of menstruation
- Occurs when the follicles have atrophied
- Plasma concentrations of oestradiol fall and concentrations of FSH and to a lesser extent LH rise due to the loss of negative feedback
- This is similar to what occurs with primary gonadal failure
- Oestrogen has an anti-parathyroid activity that is lost at menopause resulting in increased bone catabolism, oestroporosis and more brittle bones
- If HRT is given, very high levels of oestrogen may result in tachyphylaxis i.e. tolerance to dose
Pregnancy
- If the ovum has been fertilised it may implant in the endometrium
- The function of LH is then taken over by hCG which prevents involution of the corpus luteum
- Consequently levels of oestrogen and progesterone continue to rise, preventing the endometrium from sloughing off
- After the first trimester the placenta starts to produce these hormones
- During pregnancy the predominant oestrogen is oestriol
- Prolactin concentration gradually rises during the first two trimesters and then rises steeply during the last
- Prolactin, oestrogen, progesterone and hPL stimulate breast development in preparation for lactation
- High oestrogen levels inhibit milk secretion therefore lactation only occurs when plasma levels fall after delivery of the placenta
- Initially lactation depends on prolactin levels which are stimulates with suckling
- However there is still a gradual decrease in prolactin levels after delivery to reach non-pregnant by 2-3 months
- The high levels of prolactin inhibits gonadotrophin production and ovarian function resulting in a period of relative infertility
Human chorionic gonadotrophin (hCG)
- Produced by the placenta
- In early pregnancy, levels double every 2 days
- Reaches a leak at around week 13 and then falls
- The fetoplacental unit then takes over hormone production
Hyperprolactinaemia
- Causes amenorrhoea, sexual dysfunction and infertility
- High plasma levels of prolactin inhibit the pulsatile release of GnRH and thus inhibit gonadal steroid production – plasma gonadotrophin and oestrogen levels are therefore low
- 1/3 of patients with hyperprolactinaemia also have galactorrhoea
- Hyperprolactinaemia can be evoked by;
- Polycystic ovary syndrome
- Hypothyroidism
- Chronic renal failure
- Drugs;
- Pathological Oestrogen
- Dopaminergic antagonists e.g.
- Phenothiazines
- Haloperidol
- Metoclopromide
- Pathological Oestrogen
- Polycystic ovary syndrome
- Causes of hyperprolactinaemia include a prolactin secreting tumour of the pituitary gland
Polycystic Ovary Syndrome
- Commonest form of anovulatory infertility
- Plasma testosterone and androstenedione concentrations are often increased
- Plasma LH may be elevated with normal FSH
- Because plasma SHBG concentrations are reduced in the obese, the plasma concentration of free testosterone is often increased
- Plasma prolactin levels are often high
- POS is associated with insulin resistance, obesity and elevated plasma insulin concentrations which may stimulate androgen production from the ovarian theca interna cells
Hormonal changes during pregnancy
|
Hormone |
Effect |
Comment |
|
Cortisol |
increased |
Increased transcortin. Free cortisol usually normal |
|
Total T4 |
Increased |
Increased TBG. Free T4 usually normal |
|
Oestrogen |
Increased |
|
|
Progesterone |
Increased |
|
|
LH/FSH |
Decreased |
|
Hypogonadotrophic hypogonadism
- Levels of FSH and LH are low
- Causes;
- Genetic
- Kallmann’s syndrome – anosmia and GnRH deficiency
- GnRH receptor mutations
- Isolated LH or FSH deficiency
- PROP1 gene mutations that lead to absence of some pituitary hormones
- Kallmann’s syndrome – anosmia and GnRH deficiency
- Secondary causes
- Cerebral tumours e.g. craniopharyngioma, pituitary tumours, astrocytoma
- Head trauma
- Chronic systemic disease as malnutrition
- Exercise-induced amernorrhoea
- Hyperprolactinaemia
- Diabetes mellitus
- Marijuana use
- Prader-Willi syndrome
- Cerebral tumours e.g. craniopharyngioma, pituitary tumours, astrocytoma
- Genetic
- Androgens
- Increased levels cause hirsutism and virilism
- In women about half of testosterone comes from the ovaries, both by direct secretion and by conversion of androstenedione
- The rest is derived from peripheral conversion of adrenal androgens, androstenedione and dehydroepiandrostenedione
- Because there is lots of interconversion of androgens going on it can be difficult to establish the source of a rise – generally marked increases in levels of DHEA and DHEAS indicate an adrenocortical origin
- Free concentration of testosterone also depends upon levels of SHBG
- Increased levels of SHBG can be due to;
- Oestrogens
- Hyperthyroidism
- Liver disease
- Oestrogens
- Decreased levels may be due to
- Androgens
- Hypothyroidism
- Obesity
- Protein-losing disorders
- Malnutrition
- Androgens
- Causes of increased androgen levels;
- Racial
- Polycystic ovary syndrome
- Cushing’s syndrome
- Congenital adrenal hyperplasia
- Ovarian tumours; arrhenoblastomas, gonadoblastomas
- Adrenal tumours; adenomas, carcinomas
- Exogenous androgens
- Racial