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PA10315 2nd semester > Hormones of pregnancy, menopause and contraception > Flashcards

Hormones of pregnancy, menopause and contraception Flashcards

1
Q

synthesis of oestrogens/progesterone

A 
cholesterol
pregnenolone
progesterone--> (gluco,mineral)
androgens
androstenedione    testosterone
oestrone                   oestradiol
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2
Q

steroid hormones

A

tetraplanar ring
Cross membranes
Lipophilic

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3
Q

Common properties of nuclear receptors

A
  • 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)

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4
Q

Oestrogen receptors- process of binding to dna

A

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)

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5
Q

Progesterone receptors

A

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
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6
Q

Actions of oestrogens

A

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)

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7
Q

Actions of progesterone

A

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

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8
Q

Natural (endogenous) oestrogens

A

Oestradiol/oestrone

Oestriol

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9
Q

Synthetic oestrogens

A

Mestranol
Ethinylestradiol
DIethylstilbestrol

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10
Q

Availabilty of oestrogen

A

Oral, transdermal, intramuscular, implantable, topical

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11
Q

SERMs

A

Selective Estrogen receptor modulators

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12
Q

Selectively with SERMs is possible because

A

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

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13
Q

Natural progesterones

A

hydroxyprogesterone
medroxyprogesterone
dydrogesterone

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14
Q

Testosterone derivatives

A

norgestrel
desogestrel
ethynodiol

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15
Q

Availability of progesterones

A

oral, intramuscular, via vagina/rectum

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16
Q

Menopause

A

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

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17
Q

Phases of menopause

A

Perimenopuase
Menopause
Postmenopause

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18
Q

Perimenopause

A

Fluctuation in hormone levels

Can last 2-8 years

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19
Q

Menopause

A

Oestrogen levels drop

1 year after cessation of menstrual cycle

20
Q

Postmenopause

A

Oestrogen levels continue to drop

Miscellaneous health concerns begin

21
Q

Menopause symptoms

A 
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)
22
Q

Osteoporosis

A

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

23
Q

Raloxifene

A

SERM that functions like oestrogen to maintain bone density

24
Q

HRT

A

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

25
Q

HRT good effects

A

Strengthens bones
Lowers LDL
Raises HDL
Reduces menopausal symptoms eg hot flashes

26
Q

Bad effects HRT

A

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

27
Q

Vasmotor symptoms

A

Sweats, temp etc

28
Q

Contraception methods

A

Barrier:
caps
diaphragms
condoms

Intra uterine devices (IUD) “coil”

Oral:
combined hormonal contraceptives
Progeston-only contraceptives
Emergency “”

29
Q

COCs

A

Combined oestrogen/progesterone preparation for oral contraception

The pill- low dose synthetic oest/progest combinations- ve effective

Taken 21/28 d

30
Q

Role of oestrogens in COC

A

Supresses ovulation by inhibiting FSH/LH release

Mimicks normal -ve feedback effect of oestrogen at P and hypo level

31
Q

Progesterones role in COC

A

Causes thickening of cervical mucus and thins endometrium

32
Q

Mild side effects of COCs

A

Usually related to oestrogen content:

  • nausea, vomiting
  • weight gain (Na+/fluid retention)
  • mild hypertension
  • breast tenderness
33
Q

Rare toxicity associated with COC

A

Venus thromboembolism (oestrogen increases coagulation)
Stroke, heart attack (especially in heavy smokers)
Incr risk breast/cervical cancer
Amenorrhoea following withdrawal: no periods

34
Q

POC

A

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
35
Q

POC bad effects

A

Can completely suppress gonadotrophin secretion and ovulation resulting in amenorrhoea

36
Q

Emergency contraception

A 
Postcoital
levonorgestrel, ulipristal
Morning after pill
High dose progesterone
Used with 72h 98% effective
Ulipristal is a PR modulator- effective within 5 d
37
Q

Side effects of morning after pill

A

Nausea, vomiting
CV and metabolic effects
Breast tenderness

38
Q

Menstrual disorders progesterones are also used in

A

dysmenorrhoea
Menorrhagia
Premenstrual syndrome
Endometriosis

39
Q

Dysmenorrhoea

A

Painful periods, abdominal cramps

Painful contractions of uterus

40
Q

Menorrhagia

A

Heavy periods, excessive blood loss

41
Q

Premenstrual syndrome

A

Physical, psychological, behavioural symps

42
Q

Endometriosis

A

long term condition

Cells that line wall of uterus found outside it, leading to pain and discomfort

43
Q

Antiprogestogens

A

Mifepristone- PR antagonist

Used in combo with a prostaglandin- gameprost

‘medical abortion’

44
Q

Prostaglandin

A

causes uterine wall to contract

45
Q

Uterine wall contractions

A

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

46
Q

Parturition sequence

A

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

47
Q

Prostaglandins precursors

A

membrane phospholipids
Arachidonic acid
converted to prostaglandins by cyclooxygenase

PA10315 2nd semester (27 decks)

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