6. Drugs affecting reproductive function

Question 1

Where are oestrogens synthesised?

Answer 1

Ovary and the placenta

Small amounts in adrenal cortex and testis

Question 2

Clinical uses of oestrogens?

Answer 2

1. Induce artificial menstrual cycle
2. Contraception
3. At or after menopause to prevent symptoms e.g. protect against osteoporosis, vaginal dryness and flushing
4. Replacement therapy in primary ovarian failure (Turner’s syndrome) to promote sexual maturation
5. Prostate and breast cancer

Side effect: Increase risk of thromboembolism, cause feminisation in Males

Question 3

Oestrogen administration options?

Answer 3

Preparations: Oral, transdermal, intramuscular, implantable, topical (as it is well absorbed across the gut, skin and mucous membranes)

Options:
Natural e.g. Estragiol, estriol
Synthetic e.g. Menstranol, ethinylestradiol, diethylstilbestrol

Question 4

Binding of eostrogens in the blood?

Answer 4

To albumin and to a sex hormone-binding globulin.

Thus making the oestrogens inactive

Question 5

What does SERMs mean?

Answer 5

Selective Oestrogen Receptor Modulators

Question 6

What are SERMs?

Answer 6

Competitive antagonists or partial agonists of oestrogens

Question 7

3 examples of SERMs

Answer 7

Clomiphene
Tamoxifen
Raloxifene

Question 8

Action of clomiphene?

Answer 8

Acts as an oestrogen antagonist in the hypothalmus and anterior pituitary to inhibit the negative feedback to induce ovulation.

Question 9

Action of taxoxifen?

Answer 9

One such drug used in estrogen-dependent breast cancer. (anti-estrogenic action on mammary tissue)

Question 10

Acton of raloxifene?

Answer 10

Used to treat and prevent osteoporosis (estrogenic action on bone).

Question 11

3 oestrogens in the body are

Answer 11

Oestradiol **
Oestrone
Oestriol

Question 12

Progesterone secreted by..

Answer 12

Corpus luteum in mentrual cycle follicular phase

Placenta during pregnancy

Question 13

Relationship between progesterone, PR and oestrogen?

Answer 13

Progesterone acts on the PR (progesterone receptor) to regulate gene transcription in target tissues.
Oestrogen stimulates PR synthesis.
Progesterone inhibits oestrogen receptor synthesis

Question 14

What are progestins?

Answer 14

Synthetic derivatives of progesterone (as progesterone is cleared rapidly so not used therapeutically)

Question 15

3 examples of progestins?

Answer 15

Medroxyprogesterone
Hydroxyprogesterone
Norethisterone

Question 16

Therapeutic uses for progestogens?

Answer 16

1. Oral contraceptive pill alone or in combination with estrogen **
2. Used as progesterone only injectable/ implantable contraception or as part of an intrauterine contraceptive.
3. Combined with estrogen for estrogen replacement therapy in women, with an intact uterus, to prevent:
   – endometrial hyperplasia
   – carcinoma
   – endometriosis

Question 17

Danazol, what is it?

Answer 17

a modified progestogen used to treat sex- hormone dependent conditions including endometriosis, breast dysplasia and gynaecomastia

Question 18

Action of danazol?

Answer 18

Via progesterone receptor to inhibit gonadotrophin production.
So… reduces oestrogen synthesis in women and androgen synthesis in men

Question 19

Side effects of Danazol?

Answer 19

GI disturbances, weight gain, fluid retention, dizziness, headaches and menopausal symptoms
Has androgenic activity so is virilizing when given to women

Question 20

Adverse effect of progestins?

Answer 20

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

Question 21

What is midipristone and what does it do?

Answer 21

It is an anti-progestogen
In combination with prostaglandin analogues = An effective medical alternative to surgical termination to early pregnancy

Question 22

What is in the combined contraceptive pill?

Answer 22

Eoestogen in the form of: Ethinyloestradiol or mestranol

Progestogens in the form of: Noreethisterone, levonorgestrel, ethynodiol. Or in 3rd generation pills desogestrel or gestodene, these are more potent and have less andogenic action

Question 23

Mode of action of the combined pill?

Answer 23

• Estrogen 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.
• Estrogen and progestin alter endometrium to discourage implantation.
• They may also interfere with the coordinated contractions of the cervix, uterus and fallopian tubes that facilitate fertilisation and implantation.

Question 24

Side effect of the combined pill?

Answer 24

1. Mild nausea, flushing, dizziness, and bloating.
2. Weight gain, skin changes (acne or pigmentation),
   depression or irritability.
3. Amenorrhea of variable duration after cessation of taking the pill.
4. A small number of women develop reversible hypertension.
5. A small increase in the risk of thromboembolism.

Question 25

``` Progestin only contraceptive pill: Contents? Administration? MoA? Downside? Indications? ```

Answer 25

These pills include norethisterone, levonorgestrel or ethynodiol diacetate. Taken daily without interruption. MoA: • On the cervical mucous which is made inhospitable to sperm. • Hinders implantation through its effect on the endometrium and on the motility and secretions of the fallopian tubes. Downside: Contraceptive effect is less reliable than the combined pill. Indications: -Women who can't tolerate oestrogen-containing pills due to hypertension

Question 26

Action of levonogestrel?

Answer 26

- Post-coital (emergency) contraception. - Oral administration -- levonogestrel alone or in combination with estrogen - Effective if taken within 72 hours and repeated 12 hours later.

Question 27

2 examples of long-acting progestogen only contraception?

Answer 27

* Medroxyprogesterone acetate can by given intramuscularly as a contraceptive. This is effective and safe. * Levonorgestrel implanted subcutaneously. The capsules release their progestogen slowly over 5 years. * A levonorgestrel impregnated intrauterine device can last for 35 years.

Question 28

What is the process of HRT?

Answer 28

Used when ovarian function decreases and oestogen levels fall. Involves either cyclic or continuous administration of low dose oestrogens (estadiol, estriol) with or without progestogens.

Question 29

Uses of HRT?

Answer 29

* Improves the symptoms cause by reduced estrogen such as hot flushes and vaginal dryness. * Prevents and treats osteoporosis.

Question 30

Drawnbacks of HRT

Answer 30

Withdrawal bleeding Increased risk of breast cancer Increased risk of endometrial cancer (if estrogens unopposed by progesterone) Increased risk of thromboembolism.

Question 31

Main androgen is..

Answer 31

testosterone

Question 32

Testosterone synthesis?

Answer 32

By Leydig cells in testes and in smaller amounts in the adrenals and ovaries LH stimulates androgen secretion

Question 33

Clinical uses of androgens?

Answer 33

Intramuscular depot injections or patches of testosterone esters are used for replacement therapy in male hypogonadism due to pituitary or testicular disease and female hyposexuality following ovariectomy.

Question 34

Use of antiandrogens (e.g. flutamide and cryproterone)?

Answer 34

As part of the treatment of prostatic cancer as androgens promote cell division

Question 35

Used of Dihydrotestosterone synthesis inhibitors such as finasteride?

Answer 35

In benign prostatic hypertrophy.

Question 36

What anabolic steroid is used to increase protein synthesis and muscle development?

Answer 36

Nandrolone

Question 37

Uses of anabolic steroids?

Answer 37

* Androgens can be modified to alter the balance of anabolic and other effects. Such steroids (nandrolone) increase protein synthesis and muscle development. * Used in the therapy of aplastic anaemia and abused by some athletes.

Question 38

Side effect of anabolic steroids?

Answer 38

Infertility, salt and water retention, coronary heart disease and liver disease (due to difficult metabolism). Depresses HPG axis

Question 39

Name 2 gonadotrophin-releasing hormone analogues

Answer 39

Gonadorelin: The same amino acid as the endogenous form but made synthetically Nafarelin is a more potent analogue

Question 40

Describe the administration and indications of gonadotrophin-releasing hormone analogies

Answer 40

Given in pulsatile fashion will stimulate release of the gonadotrophins (FSH and LH) and induce ovulation Indications: - treatment of infertility. - Administration of GnRH in a continuous regimen will induce gonadal suppression. This is used in sex hormone-dependent conditions (e.g. prostate and breast cancers, endometriosis and large uterine fibroids).

Question 41

Uses of gonadotropins e.g. LH and FSH?

Answer 41

- Infertility due to lack of ovulation (caused by hypopituitarism following failure of treatment with clomiphene) - Male infertility d§ue to hypogonadotropic hypogonadism

Question 42

Difference between progestogen and progestin?

Answer 42

Progestogen= Broad term including progestin and progesterone Progestin= Synthetic analogue for progesterone