REB 18. Reproductive Pharmacology Flashcards
What are some of the actions of estrogen on the body?
[1] ovum maturation/timing of follicular phase
[2] preparation of uterus for implantation
[3] inhibits FSH release - negative feedback on Anterior Pituitary
[4] mineralocorticoid-like retention of Na+ and water
[5] increases coagulability of blood (increase in clots)
[6] maintains bone desnity and elasticity of skin + blood vessels
[7] induces progesterone receptors to allow progesterone response in luteal phase
What are the 2 main estrogen receptors?
[1] ER(alpha)
[2] ER(beta)
What type of hormone is estrogen? What does this mean in regards to placement of receptors?
- steroid hormone (hydrophobic)
- passes through cell membrane easily, but cannot travel in blood
- intracellular receptors!
Why is synthetic estrogen more therapeutically effective than natural estrogens? Give examples of both types of estrogen.
Natural vs. Synthetic
Natural = estradiol/estriol Synthetic = Mestranol/Stilbestrol/Ethinylestradiol
Natural estrogens are degraded more rapidly than synthetic ones. Synthetic estrogens are degraded less rapidly and so, they have a greater therapeutic effect.
Normally, estrogen is administered with another hormone….which hormone and why?
Progesterone
- if not administered with progesterone, the estrogen would be “unopposed”
- estrogen has a proliferative effect on the endometrium and so, if given without progesterone, it would increase in proliferation, increasing the chances of endometrial cancer
What is the most common synthetic estrogen?
Ethinylestradiol
What are the clinical uses of estrogen?
[1] contraception
[2] replacement therapy
- primary ovarian failure (e.g. Turner’s Syndrome)
- secondary ovarian failure (e.g. menopause)
What is an example of primary ovarian failure? What is the treatment?
example: Turner’s Syndrome
- female born with only 1 X chromosome
- treatment: estrogen + progesterone
What is an example of secondary ovarian failure? What is the treatment?
example: menopause
- treatment: hormone replacement therapy
What are some of the side effects after taking the hormone, estrogen?
- nausea + vomiting
- retention of salt + water (leads to oedema then increased blood pressue)
- increased risk of thromboembolism (due to increased coagulability)
- increased risk of uterine, ovarian + breast cancer (endometrial - due to increased cell proliferation in uterus)
- in males – leads to feminisation
What are some things that may arise when using the hormone, estrogen, as a drug? (some possible side effects and what may happen when using estrogen with another drug)
[1] estrogen-dependent tumours
- e.g. carcinoma of the endometrium or high risk of breast cancer
[2] undiagnosed genital bleeding
- may be associated with endometrial cancer
[3] liver disease
- if estrogen is not metabolized, there would be an increase in estrogen in the body
[4] history of thromboembolic disorder
[5] best avoided by heavy smokers
What is the general function of anti-estrogens?
they compete with estrogens for receptors in the target organs
- competitive binding with the natural estrogen
What are the 2 examples of estrogens?
[1] Tamoxifen
[2] Clomifene
What is Clomifene used to treat and what is its function?
- estrogen antagonist (SERM)
- induces ovulation (infertility treatment!)
- inhibits estrogen binding in anterior pituitary preventing normal negative feedback
- causes increase in FSH and LH
- stimulates the ovaries
What is Tamoxifen used to treat and what is its function?
- estrogen antagonist (SERM)
- to treat estrogen +ve breast cancer
- mild estrogen-like side effects (partial agonist on plasma lipids, endometrium + bone)
- reduction in osteoporotic fractures
What are the hormonal effects and other effects of Progestogens?
Hormonal Effects:
- maturation of endometrium
- supports gestation and embryogenesis (fetus growing in womb)
Other Effects:
- increases basal insulin + insulin response to glucose
- increases body temp
- depressant
What are some ways that progestogen may be prepared?
DO THIS
[1] Naturally Occuring Hormone
[2] Derivatives
[3] Testosterone Derivatives
What are the clinical uses of Progestogens?
[1] Contraception
[2] Hormone Replacement Therapy
[3] Endometriosis (growth of tissue-like endometrium, beyond or outside the uterus)
[4] endometrial cancer
What are some side effects of progestogens?
- weak androgenic action (e.g. acne)
- fluid retention
- weight changes
- libido changes
- depression
- premenstrual symptoms, irregular menstrual cycles
- increased risk of thromboembolism
What is the name of an anti-progestogen? How does the anti-progestogen work?
Mifepristone (RU486)
- in the presence of progesterone, it acts as a competitive receptor antagonist at the progesterone receptor
In the absence of progesterone, how does Mifepristone work?
it acts as a partial agonist at the progesterone receptors
What are the uses of Mifepristone?
- medical termination of intrauterine pregnancies
- used alone or in combination with prostaglandin E1 analogue [gemeprost or misoprostol] (it induces uterine contractions)
How long can the egg survive after ovulation to be fertilized?
12 to 24 hours
How long can sperm live in the female reproductive tract?
around 3 to 5 days (up to 5 days!)
What are some different types of hormonal contraceptives?
[1] Oral Contraceptives
(a) combined pill (estrogen + progesterone)
(b) progestogen-only pill
[2] Long-Acting Progestogen - Only
[3] Emergency (Post-Coital) Contraception
What is an example of the composition of the combined pill?
> 20ug Ethinylestradiol + >100ug Norethisterone (or Levonorgestrel)
What are the time periods that the combined pill is taken for?
- taken for 21 consecutive days
- 7 hormone free days
What is the method of action of the combined pill?
ESTROGEN:
- inhibits FSH release
- inhibits development of ovarian follicle
PROGESTOGEN:
- inhibits LH release
- prevents ovulation
- makes cervical mucus inhospitable to sperm
What is the success rate of the combined pill?
99.5%
What does it mean if the combined pill is mono-, bi- or tri- phasic?
- it refers to the concentration of estrogen and progestegon in the pill
- the concentration differs to mimic hormone concentration in the body
What are some of the side effects of using the combined pill?
- weight gain
- nausea
- mood changes
- skin pigmentation
- hypertension
- breast cancer
- thromboembolism
*side note: side effects are most limited to the first few cycles
What is an example of the composition of the progestogen-only pill (mini pill)?
- 350ug Norethisterone (Noriday)
- 75 ug Desogestrel (Cerazette) less common
What are the time periods that the progestogen-only pill (mini pill) taken for?
taken daily, NO interruption
What is the method of action of the progestogen-only pill (mini pill)?
- makes cervical mucus inhospitable to sperm
- it hinders implantations
- inhibits LH release
- prevents ovulation
What is the success rate of the progestogen-only pill?
99.0%
What are the side effects of the progestogen-only pill (mini pill)?
- irregular menstruation/amenorrhoea (no bleed at all)
- ovarian cysts a risk
When is the progestogen-only pill (mini pill)?
used where estrogen is containdicated…
- increased blood pressure with estrogen (increasd salt + water leading to oedema)
- history of venous thromboembolism (VTE)
- smokers over 35 years
- CAN BE USED BY NURSING MOTHERS!
(you cannot use estrogen-containing pills!)
What are the 2 types of long-acting progestogen only contraception?
[1] Progestogen-Only Injectables
[2] Progestogen-Only Subdermal Implant
What may Progestogen-Only Injectables be made of?
Medroxyprogesterone Acetate 150mg (DepoProvera)
How is Progestogen-Only Injectables released into circulation? How long may it be effective for?
- slowly released into the systemic circulation following intramuscular injection
- every 3 months effective
(but menstrual irregularities common!)
What is a side effect of the Progestogen-Only Injectables?
- reduction in bone mineral density and rarely, osteoporosis
- not suitable for long term use (>2 years)
What is the mechanism of action of Progestogen-Only Injectables?
- suppresses ovulation
- cervical mucus is thickened (preventing sperm penetration)
What may Progestogen-Only Subdermal Implant be made of?
Etonogestrel 68mg implanted subcutaneously non-biodegradable capsules (Implanon NXT/Nexplanon)
How is Progestogen-Only Injectables released into circulation? How long may it be effective for?
- released over 3 years
- removed no later than end of 3rd year
What is a side effect of the Progestogen-Only Subdermal Implant?
- irregular bleeding
- headaches
What is the mechanism of action of Progestogen-Only Subdermal Implant?
- suppresses ovulation
- cervical mucus is thickened (prevent sperm penetration)
What are the mechanisms of action of post-coital contraception? How does this work in the first half of cycle and the second half of cycle?
Mechanism of Action:
- delay/inhibit ovulation
- modifies cervical mucus
First Half of Cycle:
- prevents ovulation (egg not released)
Second Half of Cycle:
- if ovulation has occurred - delays movement of egg in fallopian tube and thickens cervical mucus
What are 2 examples of emergency (post-coital) contraception?
[1] Progestin-Only: Levonorgestrel (1.5 mg tablet)
[2] Ulipristal Acetate (ellaOne)
When should Levonorgestrel be used? What are some side effects? Other effects?
- must be taken within 72 hours
- efficacy decreases with time
side effect: nausea + vomiting
- weight will affect efficacy
When should Ulipristal Acetate (ellaOne) be used? What are some side effects? Other effects?
- used to prevent pregnancy up to 120 hours (5 days!)
- a progesterone receptor modulator
