Drugs Affecting Reproductive Function Flashcards
Where are oestrogens synthesised?
- Ovary and placenta
- Small amounts in adrenal cortex and testes
What are the 3 main endogenous estrogens in humans?
- Oestradiol
- Oestrone
- Oestriol
What are oestrogens main mechanism of action?
Interaction with nuclear receptors (ERa and ERB) to regulate gene transcription
What are some oestrogen effects (like rapid vascular actions) initiated by?
Interaction with membrane receptors (e.g/ GPER)
WHat do oestrogen effects depend on?
State of sexual maturity
How can artificial menstrual cycle be stimulated in a female with amenorrhea?
Given progesterone cycilcally
What can low oestrogen lead to?
Bone loss, low bone density
What can oestrogen-replacement therapy increase the risk of?
Coagulability of blood and increase the risk of thromboembolism
What menopausal symptoms can oestrogen replacement therapy protect against?
- FLushing
- Vaginal dryness
- Osteoporosis
Where can oestrogens be absorbed?
- Well absorbed from gut, across skin and mucous membranes
- Many different preparations exist (oral, transdermal, IM, implantable, topical)
What are the different natural oestrogens which can be administered?
- Estradiol
- Estriol
What are the different types of synthetic oestrogens prescribed?
- Mestranol
- Ethinylestradiol
- Diethylstilbestrol
What are oestrogens bound to in the blood?
Albumin and a sex hormone-binding globulin (active estrogen are in the unbound state)
What are the unwanted effects of estrogens?
- Breast tenderness
- nausea
- Vomiting
- Anorexia
- Retention of salt and water with resultant oedema
- Increased risk of thromboembolism
What are competitive antagonists or partial agonists of estrogens called?
Selective estrogen receptor modulators (SERMS)
What is the function of Tamoxifen?
- SERM
- Used in estrogen-dependant breast cancer
- Anti-estrogenic action on mammary tissue
What is the function of Raloxifene?
- SERM
- Used to treat and prevent post-menopausal osteoporosis (antiestrogenic effects on breat and uterus but estrogenic action on bone)
What is the function of Clomiphene?
- SERM
- Pure estrogen antagonist at the hypothalamus and pituitary
- Acts to block negative feedback which leads to increased Gonadotropin secretion, increased E2 and ovulation
What are progesterones secreted by?
- Corpus luteum in late menstraul cycle
- Placenta during pregnancy
What is used as a progestogen therapeutically instead of progesterone?
Progestins are used instead of progesterone as progesterone is cleared rapidly by the body
What are some derivatives of natural progesterone?
- Medroxyprogesterone
- Hydroxyprogesterone
What are some testosterone derivatives?
- Norethisterone
- Ethynodiol
- Desogestrel
- Gestodene (these are newer and have less androgenic activity)
What are the therapeutic uses of progestogens?
- Main therapeutic uses are in the oral contraceptive pill alone or in combination with estrogen
- Used as progesterone only injectable or implantable contraception or part of an intrauterine contraceptive
- Combined with estrogen for replacement therapy
What does progestrone combined with estrogen in replacement therapy prevent?
- Endometrial hyperplasia
- Carcinoma
- Endometriosis
What are some adverse effects of progestogens?
- Acne
- Fluid retention
- Weight gain
- Depression
- Change in libido
- Breast discomfort
- Menstraul cycle irregularity
- Increased thromboembolism
What can medication can be used as an alternative to surgical termination of early pregnancy (up to 9 wks)?
Mifepristone, in combination with prostalglandin analogues
What oestrogen is used in most combined pills?
- Ethinyloestradiol
- Mestranol
What can the progestogen be in the combined pill?
- Norethisterone
- Levonorgesterl
- Ethynodiol
- 3rd generation pills: desogestrel or gestodene (more potent and have less androgenic actions)
What is the estrogen content in a combined pill generally?
20 - 50 ug
- Advice is to use the lowest does that is well tolerated and gives good cycle control
How are most combined pills taken (what is the cycle like)?
- Taken for 21 consecutive days
- Followed by 7 days pill free to allow for a withdrawl bleed
How does estrogen inhibit the secretion of FSH?
Via negative feedback on the anteriorpituitary (results in suppression of development of ovarian follicle)
What does progestin inhibit?
LH secretion and prevents ovulation
What are the adverse effects of the combined contraceptive pill?
- Mild nausea, flushing, dizziness and bloating
- Weight gain, skin changes (acne or pigmentation), depression or irritability
- Amenrrhea of variable duration after cessation of taking the pill
- Serious withdrawl effects are rare
- A small number of women develop reversible hypertension
- Asmall increase in the risk of thromboembolism
Give examples of the progestin only contraceptive pill?
- Norethisterone
- Levonorgestrel
- Ethynodiol diacetate
What is the primary action of the progesterone only contraceptive pill?
- Primarily on cervical mucous which is made inhospitable to sperm
- Probably also hinders implantation through its effect on the endometrium and on the motility and secretions of the fallopian tubes
When are progesterone only contraceptive pills used as an alternative to the combined pill?
- When oestrogen -containing medications are contraindicated
- Suitable for women whose blood pressure rises unacceptably during treatment with combined pill
What is the downside to the progesterone only pill?
Less reliable than the combined pill
What is the post-coital (emergency) contraception?
- Oral administration of levonogesterl alone or in combination with estrogen is effective if taken within 72 hours and repeated 12 hours later
What are some of the long-acting progesterone only contraceptions?
- Medroxyprogesterone acetate can be given IM as contraception
- Levonorgestrel implanted subcutaneouly (capsules release progestogen slowly over 5 years)
- Intrauterine levonorgestrel device (can last 35 years)
What are the symptoms of menopause?
- Headaches and hot flashes
- Hair becomes thinner and loses luster
- Teeth loosen and gums recede
- Breasts droop and flatten
- Risk of CV disease
- Nipples become smaller and flatten
- Backaches
- Skin and mucous membranes become drier, skin develops a rougher texture
- Abdomen loses some muscle tone
- Body and pubic hair becomes thicker and darker
- Stress or urge incontinance
- Bones lose mass and become more fragile
- Vaginal dryness, itching and shrinking
What does postmenopausal hormone replacement therapy involve?
Either cyclic or continous administration of low dose estrogens (estradiol, estriol) with or without progestogens
- Improves symptoms caused by reduced estrogen such as hot flushes and vaginal dryness
- Prevents and treats osteoporosis
What are the drawbacks of postmenopausal hormone replacement therapy?
- Withdrawl bleeding
- Increased risk of breast cancer (risk disappears after 5 yrs of HRT)
- Increased risk of endometrial cancer (if estrogens unopposed by progesterone)
- Increased risk of thromboembolism
What is the principle androgen?
Testosterone
What hormone stimulatees androgen secretion?
LH
What are used as part of the treatment of prostatic cancer?
Antiandrogens
- Flutamide
- Cyproterone
What are IM injections or patches of testosterone esters used for?
- Replacement therapy in male hypogonadism due to pituitary or testicular disease and female hyposexuality following overiectomy
What medication is used to treat benign prostatic hypertrophy?
Dihydrotestosterine synthesis inhibitors such as finasteride
Give an example of an anabolic steroid?
Nandrolone
What can anabolic steroids such as nandrolone be used to treat?
Aplastic anaemia (abused by some athletes)
What are some side effects of anabolic steroids?
- Infertility
- Salt and water retention
- Coronary heart disease
- Liver disease
How can the reproductive axis be manipulated above the level the gonads?
Maipulate the levels of LH and FSH through giving analogues of GnRH
How many amino acids make up Gonadotrophin-releasing hormone (GnRH)?
10 (decapeptide)
What are some examples of GnRH analogues?
- Gonadorelin - same exact aa sequence as GnRH
- Nafarelin - more potent
What can GnRH analogues be used to treat?
INfertility - release of them in a pulsatile fashion will induce ovulation through stimulation of release of FSH and LH (also hypogonadotrophic hypogonadism)
- Sex-hormone dependant conditions - will induce gonadal suppression (prostate and breast cancers, endometriosis and large uterine fibroids)
How are gonadotropins made?
Through recombinant DNA technology or extracted from urine of pregnant or post-maopausal women
