Drugs Affecting Reproduction Flashcards
What are the sources of oestrogen?
- ovary
- placenta
- small amount in adrenal cortex and testis
What effects do oestrogen have on hypogonadism, amenorrhoea and menopause?
- in primary hypogonadism they stimulate development of secondary sexual characteristics and accelerate growth
- in adults with amenorrhoea given cyclically with progestogen, they induce an artificial menstrual cycle
- given at or after menopause to prevent its symptoms and protect against bone loss (but increase coagulability of blood and can cause thromboembolism)
What is the mechanism of action of oestrogens?
- interaction with nuclear receptors to regulate gene transcription (ER-alpha, ER-beta)
- some effects initiated by interaction with membrane receptors (GPER)
What are the therapeutic uses of oestrogens?
- replacement therapy in primary ovarian failure (Turner’s Syndrome) to promote sexual maturation
- replacement therapy for menopausal symptoms like flushing, vaginal dryness and osteoporosis
- in contraception
- prostate and breast cancer
- in males they cause feminisation
What are some unwanted side effects of oestrogen?
- breast tenderness
- nausea
- vomiting
- anorexia
- retention of salt and water with resultant oedema and increased risk of thromboembolism
What are anti-oestrogen drugs?
- selective oestrogen receptor modulators (SERMs)
- competitive antagonists or partial agonists of oestrogens
What are some examples of SERMs?
- tamoxifen: used in oestrogen-dependent breast cancer
- raloxifene: used to treat and prevent post-menopausal osteoporosis
- clomiphene: pure oestrogen antagonist at hypothalamus and pituitary that blocks negative feedback leading to increased gonadotropin secretion, E2 and ovulation
What are the sources and mechanism of action of progesterone?
- corpus luteum late in menstrual cycle
- placenta in pregnancy
- acts on progesterone receptor to regulate gene transcription in target tissues
- oestrogen stimulates receptor synthesis (progesterone inhibits oestrogen receptor synthesis)
What are the therapeutic uses of progestogens?
- oral contraceptive pill (either alone or in combination with oestrogen)
- progesterone only injectable or implantable contraception
- intrauterine contraceptive
- combined with oestrogen for oestrogen replacement therapy in women to prevent:
- endometrial hyperplasia
- carcinoma
- endometriosis
What are the adverse effects of progestogens?
Progestogens:
- acne
- fluid retention
- weight gain
- depression
- change in libido
- breast discomfort
- menstrual cycle irregularity
- increased thromboembolism
What is an example and use of anti-progestogens?
- mifepristone
- used in combination with prostaglandin analogues is effective medical alternative to surgical termination of early pregnancy (up to 9 weeks)
What are the common types of oestrogen and progesterone used in the combined pill?
Oestrogen::
- ethinyloestradiol
- mestranol
Progesterone:
- norethisterone
- levonorgestrel
(or if 3rd gen: desogestrel or gestodene)
Describe the mechanism of action of the combined pill
- oestrogen inhibits secretion of FSH by negative feedback on anterior pituitary
- progestin inhibits LH secretion and ovulation
- act together to alter endometrium to discourage implantation
- can interfere with coordinated contractions of cervix, uterus, and fallopian tubes that facilitate fertilisation and implantation
What are the adverse effects of the combined pill?
- mild nausea, flushing, dizziness, bloating
- weight gain, skin changes, depression
- amenorrhea variable during cessation of taking it
What are some examples of the progestin only pill?
- norethisterone
- levonorgestrel
- ethynodiol diacetate
- desogestrel
What is the mechanism of action of the progestin only pill?
- reduces LH secretion and makes cervical mucus inhospitable to sperm
- hinders implantation through its effect on the endometrium and on motility and secretions of fallopian tubes
What are some other regimens of contraception?
- emergency contraception: oral levonogestrel on its own or in combination with oestrogen within 72 hrs of unprotected sex and repeated 12 hours after
Long acting progestogen only contraception:
- levonorgestrel: subcutaneous implant (5yr) or etonogestrel subdermal implant (3yr)
- medroxyprogesterone acetate given intramuscularly
- levonorgestrel impregnated intrauterine device that can last for 35 years
What are some of the changes that occur with menopause?
- headaches and hot flushes
- hair becomes thinner
- teeth loosen and gums recede
- breasts droop and flatten
- backache
- stress/urge continence
- body and pubic hair become thicker and darker
- bones loose mass
- vaginal dryness, itching and shrinking
Describe the process of post-menopausal HRT and its pros and cons
- cyclic or continuous administration of low dose oestrogens with or without progestins
- pros: improves symptoms caused by reduced oestrogen like hot flushes, vaginal dryness and prevents and treats osteoporosis
- cons: withdrawal bleeding, increased risk of breast and endometrial cancer, increased risk of thromboembolism
What are the modes of administration and uses of androgen HRT and anti-androgens with examples?
- intramuscular depot injections or patches
- androgen HRT: used for replacement therapy in male hypogonadism due to pituitary or testicular disease and female hyposexuality following removal of ovaries
- antiandrogens (flutamide, cryproterone): prostatic cancer
What are anabolic steroids, their uses and side effects?
- androgens that have been modified to alter anabolic effects such as to increase protein synthesis and muscle development
- used for aplastic anaemia
- abused by athletes
- side effects: infertility, salt and water retention, coronary heart disease and liver disease
What are gonadotropin-releasing hormone analogues, examples and the process of administration?
- decapeptides, analogs used to manipulate the reproductive axis
- eg. gonadorelin (same as endogenous form made synthetically) and nafarelin (more potent)
- given in pulsatile fashion: stimulate release of FSH and LH inducing ovulation and used in infertility
- continuous administration: gonadal suppression for sex hormone-dependent conditions (breast/prostate cancer, endometriosis)
