PHARMACOLOGY – Reproductive Health Module
MEDICINES IN GYNAECOLOGICAL DISORDERS
1 ©AScS – 2019 A/L Batch
,PHARMACOLOGY – Reproductive Health Module
Medications used in Gynaecological Disorders
• Androgens – Testosterone, Dihydrotestosterone (DHT), Androstenedione (A), Dehydroepiandrosterone
(DHEA), Dehydroepiandrosterone sulphate (DHEAS)
• Anti-androgens – Cyproterone acetate, Finasteride, Ketoconazole, Spironolactone, Flutamide, Bicalutamide
• Oestrogens
• Anti-oestrogens – Clomiphene, Cyclofenil, Tamoxifen
• Progestogens
• Anti-progesterones – Mifepristone
• Ovarian stimulants
(01) Androgens – Testosterone, Dihydrotestosterone (DHT), Androstenedione, Dehydroepiandrosterone
(DHEA), Dehydroepiandrosterone sulphate (DHEAS)
• In women, endogenous androgens are synthesized in various tissues including the adrenal glands, ovaries,
placenta, brain and skin.
o Testosterone is synthesized in smaller amounts, by thecal cells in the ovaries and the adrenal gland.
o Half of the circulating levels of testosterone and DHT are derived from enzymatic conversion of
circulating adrenal pre-androgens (DHEAS, DHEA and A) and oestradiol.
• Androgens bind to a specific nuclear receptor in a target cell; Of these androgens, DHT has the greatest
affinity for the androgen receptor and is the most biologically potent of the endogenous androgens.
• Indications –
1. Testosterone – The only evidence-based indication for testosterone therapy in women is to treat
hypoactive sexual desire disorder after menopause. (off-label)
2. Danazol (a weak androgen) – In the treatment of endometriosis and fibrocystic breast disease.
(02) Anti-Androgens – Cyproterone acetate, Finasteride, Ketoconazole, Spironolactone, Flutamide, Bicalutamide
• Anti-androgens/androgen antagonists/testosterone blockers, are a class of drugs that prevent androgens
from mediating their biological effects in the body by,
o blocking the androgen receptor and/or
o inhibiting or suppressing androgen production.
Used in the treatment of androgen-dependent conditions in both males and females.
• Oestrogens (by inhibiting gonadotrophin secretion) and progestogens (by weak competition at androgen receptors
in target organs) are physiological antagonists to androgens.
CYPROTERONE ACETATE
• Competes with dihydrotestosterone for intracellular receptor (partial agonist).
• Chemically related to progesterone – Progesterone-like activity to inhibit LH causing antiandrogenic action.
• Used in Hirsutism, virilization and severe acne in women
• Adverse effects
o Low sex hormone levels, breast tenderness, reversible infertility, sexual dysfunction.
o Mental symptoms like depression, fatigue, and irritability.
o Rare – brain tumours.
o Increased risk of thromboembolism with oestrogens.
o Increased risk of osteoporosis without oestrogens.
(03) Oestrogens
Oestrogen – Effects on the body
• Development of normal secondary sexual characteristics in women.
• Breast – Developing mammary gland tissue and parenchymal and stromal changes at puberty.
◼ Development of mammary ducts during puberty and pregnancy, that functions to secrete breast
milk in postpartum lactation.
• Uterus – Proliferation of endometrial cells thus thickening the endometrial lining in the follicular phase, in
preparation for pregnancy.
2 ©AScS – 2019 A/L Batch
, PHARMACOLOGY – Reproductive Health Module
• Vagina – Proliferation of epithelial mucosa cells of the vagina and the vulva.
• Bone – Development of long bones and the fusion of the epiphyseal growth plates during puberty.
◼ Protects bones by inactivating osteoclast activity.
• Cardiovascular – Increasing HDL and TG levels while decreasing LDL and total plasma cholesterol and
reducing the risk of coronary artery disease with early use in postmenopausal women.
• Contraception – Suppress the release of GnRH, FSH and LH in preventing ovulation.
Oestrogen – Different Preparations
• Oestradiol and oestriol – Orally active mixed natural oestrogens.
❖ Oestradiol is the most potent and is the principal oestrogen secreted by the ovary, and it has the
highest affinity for the estrogen receptor.
❖ When given orally, the bioavailability of oestradiol is low due to first pass metabolism.
❖ The weaker endogenous oestrogens (i.e. oestradiol, estriol and estrone), or the conjugated equine
oestrogens (CEE) are preferable for physiological replacement.
• Ethinylestradiol (t 1⁄ = 13 hours) – A synthetic agent effective by mouth.
2
❖ Oestrogen of first choice for pharmacological uses (mainly contraceptive, female hypogonadism and
menstrual disorders).
• Conjugated oestrogens (Premarin) – Orally active mixed natural oestrogens, containing estrone.
• Estropipate (piperazine estrone sulphate) – Orally active synthetic conjugate.
• Diethylstilbestrol – The first synthetic oestrogen, used (rarely) in prostatic cancer and occasionally in post-
menopausal women with breast cancer.
Oestrogen – Formulations and Routes of Admission
• Oral – Easy and effective route, but is subject to the first-pass effect through the liver, and higher doses are
needed in comparison to other formulations.
• Transdermal formulations (patches and gels) – Eliminate the risk of thrombosis associated with oral route.
• Subcutaneous implants – Crystalline pellets inserted into the anterior wall or buttock release hormone over
several months. Used in women who undergo oophorectomy and hysterectomy; They are usually repeated
at 6 months and tachyphylaxis may be a problem.
• Vaginal (ring, cream, tablet or pessary) – Low-dose oestrogen is delivered for treatment of urogenital
symptoms. If used for long periods (i.e. more than 2 years), progesterone should be added to avoid
endometrial hyperplasia.
Oestrogen – Indications
• Replacement therapy in hypoestrogenaemia – Female hypogonadism and Primary ovarian insufficiency
• Post-menopausal hormone replacement therapy (HRT)
• Contraception
• Endometriosis
COCP
• Polycystic ovary syndrome
• Menorrhagia
Oestrogen – Adverse Effects
• Common adverse effects – Breast tenderness, Nausea, vomiting, Bloating, Stomach cramps, Headaches,
Weight gain and Fluid retention, Hyperpigmentation of the skin, Hair loss, Vaginal itching, Abnormal uterine
bleeding, Irritability.
• More severe adverse effects – Hypertension, Cerebrovascular accidents, Myocardial infarction, Venous
thromboembolism, Exacerbation of epilepsy, Exacerbation of asthma, Galactorrhoea, Hypocalcaemia, Risk of
endometrial cancer and breast cancer, Gallbladder disease, Hepatic haemangioma and adenoma,
Pancreatitis, Breast hypertrophy, Endometrial hyperplasia, Vaginitis and Vulvovaginal candidiasis (with
intravaginal preparations), Enlargement of uterine fibroids
3 ©AScS – 2019 A/L Batch
MEDICINES IN GYNAECOLOGICAL DISORDERS
1 ©AScS – 2019 A/L Batch
,PHARMACOLOGY – Reproductive Health Module
Medications used in Gynaecological Disorders
• Androgens – Testosterone, Dihydrotestosterone (DHT), Androstenedione (A), Dehydroepiandrosterone
(DHEA), Dehydroepiandrosterone sulphate (DHEAS)
• Anti-androgens – Cyproterone acetate, Finasteride, Ketoconazole, Spironolactone, Flutamide, Bicalutamide
• Oestrogens
• Anti-oestrogens – Clomiphene, Cyclofenil, Tamoxifen
• Progestogens
• Anti-progesterones – Mifepristone
• Ovarian stimulants
(01) Androgens – Testosterone, Dihydrotestosterone (DHT), Androstenedione, Dehydroepiandrosterone
(DHEA), Dehydroepiandrosterone sulphate (DHEAS)
• In women, endogenous androgens are synthesized in various tissues including the adrenal glands, ovaries,
placenta, brain and skin.
o Testosterone is synthesized in smaller amounts, by thecal cells in the ovaries and the adrenal gland.
o Half of the circulating levels of testosterone and DHT are derived from enzymatic conversion of
circulating adrenal pre-androgens (DHEAS, DHEA and A) and oestradiol.
• Androgens bind to a specific nuclear receptor in a target cell; Of these androgens, DHT has the greatest
affinity for the androgen receptor and is the most biologically potent of the endogenous androgens.
• Indications –
1. Testosterone – The only evidence-based indication for testosterone therapy in women is to treat
hypoactive sexual desire disorder after menopause. (off-label)
2. Danazol (a weak androgen) – In the treatment of endometriosis and fibrocystic breast disease.
(02) Anti-Androgens – Cyproterone acetate, Finasteride, Ketoconazole, Spironolactone, Flutamide, Bicalutamide
• Anti-androgens/androgen antagonists/testosterone blockers, are a class of drugs that prevent androgens
from mediating their biological effects in the body by,
o blocking the androgen receptor and/or
o inhibiting or suppressing androgen production.
Used in the treatment of androgen-dependent conditions in both males and females.
• Oestrogens (by inhibiting gonadotrophin secretion) and progestogens (by weak competition at androgen receptors
in target organs) are physiological antagonists to androgens.
CYPROTERONE ACETATE
• Competes with dihydrotestosterone for intracellular receptor (partial agonist).
• Chemically related to progesterone – Progesterone-like activity to inhibit LH causing antiandrogenic action.
• Used in Hirsutism, virilization and severe acne in women
• Adverse effects
o Low sex hormone levels, breast tenderness, reversible infertility, sexual dysfunction.
o Mental symptoms like depression, fatigue, and irritability.
o Rare – brain tumours.
o Increased risk of thromboembolism with oestrogens.
o Increased risk of osteoporosis without oestrogens.
(03) Oestrogens
Oestrogen – Effects on the body
• Development of normal secondary sexual characteristics in women.
• Breast – Developing mammary gland tissue and parenchymal and stromal changes at puberty.
◼ Development of mammary ducts during puberty and pregnancy, that functions to secrete breast
milk in postpartum lactation.
• Uterus – Proliferation of endometrial cells thus thickening the endometrial lining in the follicular phase, in
preparation for pregnancy.
2 ©AScS – 2019 A/L Batch
, PHARMACOLOGY – Reproductive Health Module
• Vagina – Proliferation of epithelial mucosa cells of the vagina and the vulva.
• Bone – Development of long bones and the fusion of the epiphyseal growth plates during puberty.
◼ Protects bones by inactivating osteoclast activity.
• Cardiovascular – Increasing HDL and TG levels while decreasing LDL and total plasma cholesterol and
reducing the risk of coronary artery disease with early use in postmenopausal women.
• Contraception – Suppress the release of GnRH, FSH and LH in preventing ovulation.
Oestrogen – Different Preparations
• Oestradiol and oestriol – Orally active mixed natural oestrogens.
❖ Oestradiol is the most potent and is the principal oestrogen secreted by the ovary, and it has the
highest affinity for the estrogen receptor.
❖ When given orally, the bioavailability of oestradiol is low due to first pass metabolism.
❖ The weaker endogenous oestrogens (i.e. oestradiol, estriol and estrone), or the conjugated equine
oestrogens (CEE) are preferable for physiological replacement.
• Ethinylestradiol (t 1⁄ = 13 hours) – A synthetic agent effective by mouth.
2
❖ Oestrogen of first choice for pharmacological uses (mainly contraceptive, female hypogonadism and
menstrual disorders).
• Conjugated oestrogens (Premarin) – Orally active mixed natural oestrogens, containing estrone.
• Estropipate (piperazine estrone sulphate) – Orally active synthetic conjugate.
• Diethylstilbestrol – The first synthetic oestrogen, used (rarely) in prostatic cancer and occasionally in post-
menopausal women with breast cancer.
Oestrogen – Formulations and Routes of Admission
• Oral – Easy and effective route, but is subject to the first-pass effect through the liver, and higher doses are
needed in comparison to other formulations.
• Transdermal formulations (patches and gels) – Eliminate the risk of thrombosis associated with oral route.
• Subcutaneous implants – Crystalline pellets inserted into the anterior wall or buttock release hormone over
several months. Used in women who undergo oophorectomy and hysterectomy; They are usually repeated
at 6 months and tachyphylaxis may be a problem.
• Vaginal (ring, cream, tablet or pessary) – Low-dose oestrogen is delivered for treatment of urogenital
symptoms. If used for long periods (i.e. more than 2 years), progesterone should be added to avoid
endometrial hyperplasia.
Oestrogen – Indications
• Replacement therapy in hypoestrogenaemia – Female hypogonadism and Primary ovarian insufficiency
• Post-menopausal hormone replacement therapy (HRT)
• Contraception
• Endometriosis
COCP
• Polycystic ovary syndrome
• Menorrhagia
Oestrogen – Adverse Effects
• Common adverse effects – Breast tenderness, Nausea, vomiting, Bloating, Stomach cramps, Headaches,
Weight gain and Fluid retention, Hyperpigmentation of the skin, Hair loss, Vaginal itching, Abnormal uterine
bleeding, Irritability.
• More severe adverse effects – Hypertension, Cerebrovascular accidents, Myocardial infarction, Venous
thromboembolism, Exacerbation of epilepsy, Exacerbation of asthma, Galactorrhoea, Hypocalcaemia, Risk of
endometrial cancer and breast cancer, Gallbladder disease, Hepatic haemangioma and adenoma,
Pancreatitis, Breast hypertrophy, Endometrial hyperplasia, Vaginitis and Vulvovaginal candidiasis (with
intravaginal preparations), Enlargement of uterine fibroids
3 ©AScS – 2019 A/L Batch
