Hormones of pregnancy, menopause and contraception Flashcards
synthesis of oestrogens/progesterone
cholesterol pregnenolone progesterone--> (gluco,mineral) androgens androstenedione testosterone oestrone oestradiol
steroid hormones
tetraplanar ring
Cross membranes
Lipophilic
Common properties of nuclear receptors
- have ligand binding and dna binding domains
- translocate to nucleus once hormone bound
- Bind to Hormone response elements (recognition elements) in specific gene sequences
- Dimerization important for function- hormone binds to dna and forms dimers
Androgen receptors (AR), Estrogen receptors (ER), Progesterone receptors (PR)
Oestrogen receptors- process of binding to dna
Changes conformation due to dissociation of heat shock proteins after oestrogen binds
Receptor undergoes dimerization in order for incr affinity for dna
Oestrogen-receptor complex can now bind to specific DNA sites- EREs(oestrogen response/recognition elements)
Progesterone receptors
Nuclear receptors regulating gene transcription
Bind to PREs
Two isoforms- PR-A and PR-B:
- identical ligand binding
- bring about different effects
- PR-B mediates the stimulatory effects of progesterone
Actions of oestrogens
Produced by ovaries, act on uterus: stimulation of endometrium, thickening of vaginal mucosa, thinning of cervical mucus (allows sperm to reach egg)
Hypothalamus: incr GnRH secretion
Pituitary: decr LH secretion
Metabolism: Protein anabolism, bone growth, decr circulating cholesterol (higher risk of cvd in menopause)
Female sex characteristics: Secondary sex characteristics (hair growth, breast development)
Actions of progesterone
Produced in luteal phase, decreases GnRH production
Induction of secretory activity in oestrogen-primed endometrium
Incr viscosity of cervical mucous (for implantation of egg, stops other sperm)
Promotes glandular breast development
Incr basal body temp
Natural (endogenous) oestrogens
Oestradiol/oestrone
Oestriol
Synthetic oestrogens
Mestranol
Ethinylestradiol
DIethylstilbestrol
Availabilty of oestrogen
Oral, transdermal, intramuscular, implantable, topical
SERMs
Selective Estrogen receptor modulators
Selectively with SERMs is possible because
ER-alpha and/or ER-beta show differential tissue expression
Conformation dependent bind to DNA and TFs
Tissue dependent responses ranging between pro-oestrogenic, partially oestrogenic and anti-oestrogenic effects
Role in treatment of certain cancers
Natural progesterones
hydroxyprogesterone
medroxyprogesterone
dydrogesterone
Testosterone derivatives
norgestrel
desogestrel
ethynodiol
Availability of progesterones
oral, intramuscular, via vagina/rectum
Menopause
Menstruation irregular then ceases
Few primadorial follicles left in ovaries- no follicles = no oestrogen
Gonadotropins secreted in greater amounts, because of loss of -ve feedback
Phases of menopause
Perimenopuase
Menopause
Postmenopause
Perimenopause
Fluctuation in hormone levels
Can last 2-8 years
Menopause
Oestrogen levels drop
1 year after cessation of menstrual cycle
Postmenopause
Oestrogen levels continue to drop
Miscellaneous health concerns begin
Menopause symptoms
Lower oestrogen levels lead to: hot flushes of skin (unopposed progesterone driving incr in temp, sympathetic activation) Night sweats Palpatations Incr irritability Mood changes Vaginal atrophy Development of osteoporosis (incr risk of hip and spine fractures)
Osteoporosis
oestrogen maintains bone mineral density
+ve relationship between maintenance of bone mass and HRT with oestrogen:
- decr rates of wrist, non-vertebral, vertebral and hip fractures
Raloxifene
SERM that functions like oestrogen to maintain bone density
HRT
Generally use natural oestrogen , not synthetic
Oestrogen and progesterones in women with a intact uterus
Oral, transdermal, vaginally, subcutaneous implant
HRT long term can reduce post-menopausal osteoporosis and vasomotor symptoms
Oestrogens decr LDL levels but mixed evidence about decr rish of CHD
HRT good effects
Strengthens bones
Lowers LDL
Raises HDL
Reduces menopausal symptoms eg hot flashes
Bad effects HRT
Incr risk of breast cancer (especially if just using oestrogen- bc causes breast development)
Incr blood clot risk
Incr risk of uterine cancer can be reduced by using progesterone along with oestrogen
Vasmotor symptoms
Sweats, temp etc
Contraception methods
Barrier:
caps
diaphragms
condoms
Intra uterine devices (IUD) “coil”
Oral:
combined hormonal contraceptives
Progeston-only contraceptives
Emergency “”
COCs
Combined oestrogen/progesterone preparation for oral contraception
The pill- low dose synthetic oest/progest combinations- ve effective
Taken 21/28 d
Role of oestrogens in COC
Supresses ovulation by inhibiting FSH/LH release
Mimicks normal -ve feedback effect of oestrogen at P and hypo level
Progesterones role in COC
Causes thickening of cervical mucus and thins endometrium
Mild side effects of COCs
Usually related to oestrogen content:
- nausea, vomiting
- weight gain (Na+/fluid retention)
- mild hypertension
- breast tenderness
Rare toxicity associated with COC
Venus thromboembolism (oestrogen increases coagulation)
Stroke, heart attack (especially in heavy smokers)
Incr risk breast/cervical cancer
Amenorrhoea following withdrawal: no periods
POC
Progesterone only contraceptive
Less reliable than COC
Effects:
- cervical mucus thick and sticky- no sperm
- Endometrium changes, making implantation less likely
- Weak -ve feedback inhibition of LH release and ovulation
POC bad effects
Can completely suppress gonadotrophin secretion and ovulation resulting in amenorrhoea
Emergency contraception
Postcoital levonorgestrel, ulipristal Morning after pill High dose progesterone Used with 72h 98% effective Ulipristal is a PR modulator- effective within 5 d
Side effects of morning after pill
Nausea, vomiting
CV and metabolic effects
Breast tenderness
Menstrual disorders progesterones are also used in
dysmenorrhoea
Menorrhagia
Premenstrual syndrome
Endometriosis
Dysmenorrhoea
Painful periods, abdominal cramps
Painful contractions of uterus
Menorrhagia
Heavy periods, excessive blood loss
Premenstrual syndrome
Physical, psychological, behavioural symps
Endometriosis
long term condition
Cells that line wall of uterus found outside it, leading to pain and discomfort
Antiprogestogens
Mifepristone- PR antagonist
Used in combo with a prostaglandin- gameprost
‘medical abortion’
Prostaglandin
causes uterine wall to contract
Uterine wall contractions
caused by oxytocin and prostaglandin
Progesterones cause relaxation and maintain cervical length: habitual miscarriage, premature labour
Beta2- adenoreceptor agonists inhibit contractions of the pregnant uterus
Parturition sequence
Posterior pituitary releases oxytocin, which causes uterine contraction
Contraction releases prostaglandin, +vely feeds back to cause more contraction
Contraction pushes baby’s head downwards and leads to cervical stretch, which reinforces contraction and +ve feeds back onto pituitary
Prostaglandins precursors
membrane phospholipids
Arachidonic acid
converted to prostaglandins by cyclooxygenase
