Lecture 57: Oestrogen and Progesterone

how are osteogens and progesterone synthesised?

cholesterol—>pregnenalone —→ progesterone——>androgens——> androstenediones and testosterone——→ oestrone and oestradiol

how do sex hormones bind to nuclear receptors?

• steroid hormones bind to the nuclear receptors binding site in the cytoplasm

• they then translocate to the nucleus

• the receptors dimerise to regulate gene transcription

• the receptors bind to the docking site on the DNA for the hormone response element

how do oestrogen receptors act?

• oestrogen binds to the ERalpha or ERbeta

• the receptor changes its conformation due to dissociation from the heat

• the receptors dimerise in order to increase affinity for binding to the DNA ( binds to specific oestrogen response elements)

• ERbeta receptors also produce a nongenomic response

how do progesterone receptors act?

• they have 2 isoforms as they are the same gene

• PR- A and PR- B

• PR- B brings about the stimulatory effect of progesterone

• they bind to progesterone response elements and regulate gene transcription

what does oestrogen do in the body?

• stimulates endometrium, thickens vaginal mucosa and thins cervical mucus

• secondary sex characteristics for women, breast duct growth

• increases protein and bone production, and lowers cholesterol

• decreases GnRH in hypothalamus, but increases it in ovaries, lowers LH in the pituitary

• multiple effects on CNS

what does progesterone do in the body?

• lowers GnRH production in the luteal phase as corpus luteum produces progesterone

• stimulates the secretory phase of the endometrium

• increases thickness of cervical mucus, increases glandular breast development and basal body temp

• basal body temp can be used to indicate for ovulation

what are the natural and synthetic oestrogen preparations?

natural: Oestradiol, oestrone , oestriol

synthetic: ethinylestradiol

forms: oral, transdermal, IM, implant, topical

Selective oestrogen receptor modulators are used in cancer treatment and are selective due to ER-alpha/beta tissue expression

what are some of the natural and testosterone derived progesterone treatments?

natural: 17- alpha- hydroxyprogesterone

testosterone-derived: levonorgestrel

what are the features of menopause?

• changes in hormone levels

• due to ovarian failure, loss of sensitivity to FSH and LH

• there are no more developing follicles, so no more oestrogen, no more eggs and no more progesterone

what are the phases of menopause?

1. perimenopause- hormone fluctuations start 2-8 years

2. menopause- oestrogen levels drop, official once its been 1 year since last period

3. postmenopause- oestrogen levels continue to decline

• this can increase risk of CVD, stroke, Osteoporosis and dementia

symptoms of menopause:

• hot flushes

• vaginal dryness

• osteoporosis

• heart palpitations

what is osteoporosis and what can be taken to help once it starts?

• decrease in bone density as oestrogen maintains bone density

• HRT can be given to reduce fracture risk

• raloxifene mimics oestrogen to maintain bone

what is HRT?

• hormone replacement therapy

• uses natural oestrogens

• combo of oestrogens and progesterones

• can be a tablet, patch, gel, spray, IUD

progesterones are given with oestrogens in HRT to counteract the stimulatory effects of oestrogen to prevent uterine cancer

what are the positive effects of HRT?

• strengthens bone

• lowers cholesterol

• reduces menopausal symptoms

reduces osteoporosis

what are the negative effects of HRT?

• increases breast and uterine cancer risk

• increases blood clot risk

benefits outweigh risks

what are the contraception types?

barrier: condoms, caps

IUD: coil

oral: combined, progesterone only, emergency contraception

what are the features of combined oral contraceptives?

• ethinylestradiol+ progestogen OR levonorgestrel + desogestrel

• take 21/28 day cycles

• oestrogen inhibits the secretion of FSH so no eggs develop

• progesterone inhibits secretion of LH from pituitary leading to thickened cervical mucus and thin endometrium

what are the side effects of combined oral contraceptives?

mild: nausea, weight gain, hypertension

serious: VTE, Myocardial infarction

increases breast C risk, decreases ovarian C risk

may cause amenorrhea after stopping

what are progesterone only contraceptives?

• levonorgesterol

• taken continously

• thickens cervical mucus, thins endometrium

• may stop ovulation

• useful when oestrogen is contraindicated

menstrual disorders treated with progestogens:

• dysmenorrhoea- painful periods, abdominal cramps

• menorrhagia- heavy periods, excessive bleeding

• PMS

• Endometriosis- cells behave like lining outside uterus

what are the features of occasional contraception?

• high dose progesterone- levonorgesterel, within 3 days 98% effective)

• ulipristal(PR modulator): within 5 days

• side effects: nausea vomitting

• copper IUD can cause sperm/ova toxicity

what are antiprogesterones?

• medical abortion alternative to surgery

• Mifepristone(PR antagonist) and misoprostol(PGE1 analogue)

how are prostaglandins made and what do they do?

• phospholipase A causes membrane phospholipid to become arachidonic acid

• arachidonic acid becomes prostaglandins via cyclooxygenase

uterine contractions are stimulates by prostaglandins

how do uterine wall contractions happen?

• oxytocin and PG are labour inductors

• progestogens relax uterus and maintain cervix; used in habitual miscarriage and perterm labour

• B2 agonists inhibit contractions