Drugs Affecting Reproduction Function Flashcards
Where is estrogen produced ?
Synthesised by the ovary and the placenta and in small amounts in the adrenal cortex and testis.
Identify the main endogenous estrogen of the body. How many types of estrogens are there ?
There are 3 main endogenous oestrogens in humans.
Oestradiol is the most potent and principal oestrogen
Which types of receptors does estrogen usually interact with ?
- Main mechanism of action involves interaction with nuclear receptors (ERα and ERβ) to regulate gene transcription.
- Some estrogen effects (rapid vascular actions) are initiated by interaction with membrane receptors (e.g. GPER)
What is the primary factors influencing the kind of effects of estrogen.
Effects of estrogen depend on the state of sexual maturity
Identify the main therapeutic uses of estrogen.
- Replacement therapy in primary ovarian failure (Turner syndrome) to promote sexual maturation.
- Replacement therapy for menopausal symptoms such as flushing, vaginal dryness and osteoporosis.
- In contraception, they are used singly or in combination with progestogens.
- Prostate and breast cancer.
- When administered to males they cause feminisation.
Identify the main natural, and synthetic estrogen preparations which exist.
Natural: estradiol, estriol
Synthetic: mestranol
Identify the main unwanted effects of estrogen.
Unwanted effects of estrogens include: breast tenderness, nausea, vomiting, anorexia, retention of salt and water with resultant oedema and increased risk of thromboembolism
Identify the main kinds of drugs which affect reproductive function.
- Estrogens
- Selective Estrogen Receptor Modulators (SERMs)
- Progestogens
- Contraceptive Pills (including CCP, Progestin Only Contraceptive Pill, Post-coital (emergency) contraception, Long-acting progestogen only contraception)
- Post menopausal hormone replacement therapy
- Androgens (and antiandrogens)
- Anabolic Steroids
- Gonadotrophin-releasing hormone analogues
What is the mode of action of Selective Estrogen Receptor Modulators (SERMs) ?
Competitive antagonists or partial agonists of oestrogens are called selective oestrogen receptor modulators (SERMs).
(this includes some drugs that are selective oestrogen agonists in some tissues but antagonists in others)
Identify the main SERMs.
- Tamoxifen
- Raloxifene
- Clomiphene
State the main therapeutic uses of Tamoxifen. Is this an estrogen agonist or antagonist ?
Oestrogen-dependent breast cancer (anti-oestrogenic action on mammary tissue)
So selective oestrogen agonists in some tissues but antagonists in others.
State the main therapeutic uses of Raloxifene. Is this an estrogen agonist or antagonist ?
Used to treat and prevent post- menopausal osteoporosis (antiestrogenic effects on breast and uterus but oestrogenic action on bone)
So selective oestrogen agonists in some tissues but antagonists in others.
What is the mode of action of Clomiphene ? Is this an estrogen agonist or antagonist ?
Pure estrogen antagonist at the hypothalamus and pituitary - acts to block negative feedback which leads to increased gonadotropin secretion, increased E2 and ovulation.
Where and when is progesterone secreted ?
Progesterone is secreted by the corpus luteum late in the menstrual cycle and by the placenta during pregnancy.
Which receptors does progesterone act on ? What is its exact mode of action ?
Acts on the progesterone receptor (PR) to regulate gene transcription in target tissues.
Progesterone inhibits the synthesis of oestrogen receptors (after estrogen stimulates synthesis of PR)
To what extent is progesterone used therapeutically ?
• Progesterone is not used therapeutically due rapid clearance. Instead synthetic deriviatives are used – called progestins.
Identify progestogens used therapeutically.
PROGESTINS:
Medroxyprogesterone (derivative of natural progesterone)
Norethisterone (testosterone derivatives)
Distinguish between progestin and progestogen and progesterone.
Progestins are synthetic progestogens and are used in medicine
Progesterone is also an endogenous progestogen
Identify therapeutic uses of progestogens.
1) Main therapeutic uses are in the oral contraceptive pill alone or in combination with oestrogen
2) Used as progesterone only injectable or implantable contraception or part of an intrauterine contraceptive.
3) Combined with oestrogen for oestrogen replacement therapy in women, with an intact uterus, to prevent:
– endometrial hyperplasia
– carcinoma
– endometriosis
Identify any unwanted side effects of progestogens.
Adverse effects of progestogens include: acne, fluid retention, weight gain, depression, change in libido, breast discomfort, menstrual cycle irregularity and increased thromboembolism.
Identify an anti-progestogen, and a therapeutic use of this anti-progestogen.
The anti-progestogen, mifepristone, in combination with prostaglandin analogues is an effective medical alternative to surgical termination of early pregnancy (up to 9 wks).
What are the main components of the combined contraceptive pill ?
-Oestrogen in most combined pills is ethinyloestradiol or
mestranol.
-The progestogen can be norethisterone, levonorgestrel, ethynodiol or in 3rd generation pills desogestrel or gestodene (more potent and have less androgenic actions).
What is the normal dose of combined contraceptive pill ? How often is this taken ?
Advice is to use the lowest dose that is well tolerated and gives good cycle control.
Most combined pills are taken for 21 consecutive days followed by 7 days pill free to allow a withdrawal bleed.
What is the consequence of discontinuation of the combined contraceptive pill ?
Menstrual cycles return quickly after discontinuation.
Describe the mechanism of action of combined contraceptive pill.
- Oestrogen inhibits the secretion of FSH via negative feedback on the anterior pituitary and thus suppresses development of the ovarian follicle.
- Progestin inhibits LH secretion and prevents ovulation.
Identify any adverse effects of the combined contraceptive pill.
- Mild nausea, flushing, dizziness, and bloating.
* Amenorrhea of variable duration after cessation of taking the pill.
Identify examples of progestin only contraceptive pills.
Norethisterone (testosterone derivative), Levonorgestrel
How often is the progestin only contraceptive pill taken ?
The pill is taken daily without interruption.
Describe the mechanism of action of progestin only contraceptive pills.
1) The mode of action is primarily on the cervical mucous which is made inhospitable to sperm.
2) Probably also hinders implantation through its effect on the endometrium and on the motility and secretions of the fallopian tubes.
When is progestin only contraceptive pill used, rather than the combined contraceptive pill ?
They offer a suitable alternative to women in whom oestrogen-containing pills are contraindicated and are suitable for women whose blood pressure rises unacceptably during treatment with the combined pill.
Identify drug regimens for contraception other than combined contraceptive pill and progestin only contraceptive.
1) Post-coital (emergency) contraception (levonogestrel)
2) Long-acting progestogen only contraception (Medroxyprogesterone acetate, Levonorgestrel)
Describe the time and method of administration of post-coital (emergency) contraception.
Oral administration of levonogestrel alone or in combination with oestrogen is effective if taken within 72 hours and repeated 12 hours later.
Describe the time and method of administration of Long-acting progestogen only contraception.
1) Medroxyprogesterone acetate can by given intramuscularly as a contraceptive.
2) Levonorgestrel implanted subcutaneously. The capsules release their progestogen slowly over 5 years.
Identify the main symptoms of menopause. Why do these occur ?
- Headache and Hot Flashes
- Hair becomes thinner and loses luster
- Breasts droop and flatten
- Risk of CV disease
- Backache
- Body and pubic hair becomes darker and thicker
- Bones lose mass and become more fragile
- Vaginal dryness, itching, and shrinking
Because at menopause ovarian function decreases and estrogen levels fall
Identify any treatments for the symptoms associated with menopause.
Postmenopausal hormone replacement therapy
How does Postmenopausal hormone replacement therapy consist of ? How large are the doses administered and how often are they administered ?
HRT normally involves either cyclic or continuous administration of low dose estrogens (estradiol, estriol) with or without progestogens.
Which symptoms of menopause does Postmenopausal hormone replacement therapy target ?
- Improves the symptoms cause by reduced estrogen such as hot flushes and vaginal dryness
- Prevents and treats osteoporosis.
What are the main unwanted side effects of postmenopausal hormone replacement therapy ?
Withdrawal bleeding, increased risk of breast cancer, increased risk of endometrial cancer (if estrogens unopposed by progesterone), increased risk of thromboembolism.
Where is testosterone secreted ?
Synthesised by Leydig cells in testes and in smaller amounts in the adrenals and ovaries.
Identify effects of testosterone on various body parts.
Brain: libido, aggression
Skin: hair growth, sebum production, balding
Liver: synthesis of serum proteins
Male sexual organs: penile growth, spermatogenesis, prostate growth and function
Muscle: increase in strength and V
Kidney: stimulation of EPO prod
Bone: Accelerated linear growth + closure of epiphyseal plates
Bone marrow: stimulation of stem cells
ANDROGENS
- Indications
- Effects
- Mechanism of action
ANDROGENS
Indications: replacement therapy in male hypogonadism due to pituitary or testicular disease and female hyposexuality following ovariectomy
-Effects: include development of male secondary sex characteristics in pre-pubertal men and masculinisation of women
-Mechanism of action: via nuclear receptors and control of gene expression
Identify the main antiandrogens, and the indications of each.
Flutamide used as part of the treatment of prostatic cancer.
Dihydrotestosterone synthesis inhibitors such as finasteride are used in benign prostatic hypertrophy.
(all antiandrogens)
How are anabolic steroids related to sex hormones ?
Androgens can be modified to alter anabolic and other effects (i.e. anabolic steroids are androgen derivatives)
What are the main effects, and indications, of anabolic steroids ? Give an example of one.
Effects: Increase protein synthesis and muscle development
Indications: Used in the therapy of aplastic anaemia (also abused by some athletes)
E.g. Nandrolone
Identify side effects of anabolic steroids.
- Infertility
- Salt and water retention
- Coronary heart disease
- Liver disease.
Which type of peptide is GnRH ?
Decapeptide
Identify examples of Gonadotrophin-releasing hormone analogues. Which of these is a more potent analogue ?
• Nafarelin
How are GnRH analogues administered ? What are the indications for GnRH analogues ?
1) Given in pulsatile fashion will stimulate release of the gonadotrophins (FSH and LH) and induce ovulation, used in the treatment of infertility.
2) Administration of GnRH in a continuous regimen will induce gonadal suppression (similarly to what GnRH antagonists would do). This is used in sex hormone-dependent conditions (e.g. prostate and breast cancers, endometriosis and large uterine fibroids).
What are the main indications for gonadotropin preparations ?
1) infertility caused by lack of ovulation as a result of hypopituitarism following failure of treatment with clomiphene
2) men with infertility due to hypogonadotropic hypogonadism
