Drugs Affecting the Reproductive System

Question 1

What are the three main oestrogens in the human body?

Answer 1

Oestrodiol (most potent), oestrone and oestriol

Question 2

What is the main mechanism of action of oestrogen

Answer 2

• They interact with nuclear receptors to regulate gene transcription but some oestrogen effects are initiated by interaction with membrane receptors.

Question 3

What are the theraputic uses of oestrogen?

Answer 3

• Replacement therapy in primary ovarian failure to promote sexual maturation,
• Replacement therapy for menopausal symptoms,
• Contraception (alone or in combo with progesterones),
• In prostate and breast cancer,
• To cause feminisation in males

Question 4

Name some natural and synthetic oestrogens

Answer 4

Natural - oestradiol and oestriol.

Synthetic - menstranol, ethinylestradiol, diethylstilbestrol

Question 5

How does oestrogen travel in the blood?

Answer 5

Bound to albumin and to a sex hormone-binding globulin (active oestrogens are in the unbound state)

Question 6

What are the unwanted side effects of oestrogens

Answer 6

• breast tenderness,
• Nausea,
• Vomiting,
• Anorexia,
• Retention of salt and water with resultant oedema,
• Risk of thromboembolism

Question 7

What are selective oestrogen receptor modulators and name some examples (SERMS)?

Answer 7

Competative antagonists or partial agonists of oestrogens. eg,

• Tamoxifen (used in oestrogen dependant breast cancer),
• Raloxifene (for post-menopausal oesteoporosis)
• Clomiphene (oestrogen anatgonist = increased gonadotrophin secretion and increased ovulation)

Question 8

What is the function of progestogens

Answer 8

They are secreted by the corpus luteum late in the menstrual cycle and by the placenta. It acts on progesterone receptors to regulate gene transcription. It is then cleared rapidly by the liver

Question 9

How to oestrogens and progestogens effect eachothers receptors?

Answer 9

Oestrogen stimulates synthesis of progesterone receptors and progesterone inhibits synthesis of oestrogen receptors

Question 10

Name examples of natural and testosterone derived progestogens

Answer 10

Natural - hydroxyprogesterone and medroxyprogesterone.

Testosterone derived - norethisterone and newer progestogens eg, desogestrel and gestodene.

Question 11

What are the theraputic uses of progestogens?

Answer 11

• Oral contraceptive pill (combined or on its one),
• Progesterone only injectable, implantable contraception or part of intrauterine contraceptive.
• Combined with oestrogen for oestrogen replacement therapy to prevent endometrial hyperplasia, carcinoma or endometriosis.

Question 12

What are the adverse effects of progestogens

Answer 12

Acne, fluid retention, weight gain, depression, change in libido, breast discomfort, menstrual cycle irregularity and increased risk of thromboembolism.

Question 13

When are anti-progestogens used?

Answer 13

eg mifepristone, in combination with prostaglandin analogues is an effective medical an effective medical alternative to surgical termination of early pregnancy

Question 14

What are the most common oestrogens and progestogens in the combined contraceptive pill

Answer 14

Oestrogens - Ethinyloestradiol or mestranol.

Progestogens - Norethisterone, levonorgestrel, ethynodiol or the 3rd generation pills eg, desogestral or gestodene

Question 15

Describe the mode of action of the combined pill

Answer 15

The oestrogen inhibits secretion of FSH via negative feedback on the anterior pituitary, prevents development the ovarian follicle.
Progestin inhibits LH secretion and prevents ovulation.
Both act in concert to alter the endometrium is such a way to discourage implantation. May also interfere with coordinated contractions.

Question 16

What are some adverse side effects of the combined contraceptive pill?

Answer 16

• Mild nausea, flushing, dizziness and bloating.
• Weight gain, skin changes, depression or irritability,
• Amenorrhoea,
• Small risk of hypertension,
• Small risk of thomboembolism

Question 17

What is the mechanism of the progesterone only pills

Answer 17

It reduces LH secretion making the mucous inhospitable to sperm and hinders implantation through its effects on the endometrium and on motility and secretion. Good alternative to women where oestrogen is contraindicated.

Question 18

Describe features of the post-coital contraception

Answer 18

Oral administration of levonogestrel alone in combo with oestrogen and is effective if taken within 72 hours and repeated 12 hours later

Question 19

What are some long-acting progestogen only contraception?

Answer 19

• Levonorgestrel (norplant) - subcutaneous implant for 5 years.
• Etonogestrel (nexplanon) - subdermal implant for 3 years.
• Medroxyprogesterone acetate - IM injection

Question 20

What are some symptoms of the menopause

Answer 20

• Headaches and hot flushes,
• Teeth loosen and gums recede,
• Hair becomes thinner,
• Breasts droop and flatten,
• Risk of cardiovascular disease,
• backaches,
• Vaginal dryness, itching and shrinking,
• Skin becomes drier,
• Abdomen looses muscle tone,
• Loss of bone mass density

Question 21

How can menopausal symptoms be treated and what are some of its drawbacks?

Answer 21

Hormone replacement therapy involving cyclic or continuous administration of low dose oestrogens with/without progestogens.
drawbacks include withdrawal bleeding, increased risk of breast cancer, increased risk of endometrial cancer and increased risk of thromboembolism.

Question 22

What are IM or transdermal patches of testosterone esters used for?

Answer 22

Replacement therapy in male hypogonadism due to pituitary or testicular disease and in female hyposexuality following removal of ovaries.

Question 23

Name some examples of anti-androgens and what they are used for

Answer 23

eg, flutamide which is used in the treatment of prostatic cancer.
- Dihydrotestosterone synthesis inhibitors such as finasteride which is used in benign prostatic hypertrophy.

Question 24

Name an example of an anabolic steroid and its effects

Answer 24

Nandrolone which increases muscle synthesis and muscle development. It is used in aplastic anaemia but unwanted effects are infertility, salt and water retention, coronary heart disease and liver disease

Question 25

Name some examples of gonadotrophin-releasing hormone analogues and what they are used for

Answer 25

Gonadorelin and nafarelin. When given in a pulsatile fashion it will stimulate release of gonadotrophins to induce ovulation, used in treatment of infertility. If given in continuous regimen, it will induce gonadal supression (used in prostatic/breast cancers, endometriosis ect)

Question 26

What are gonadotrophins used for?

Answer 26

Treat infertility caused by lack of ovulation as a result of hypopituitarism following failure of clomiphene or to treat male infertility due to hypogonadotropic hypogonadism