Sex hormone responsive conditions

Question 1

Oestrogens are necessary for

Answer 1

the development of female secondary sexual characteristics.

Question 2

The natural and synthetic oestrogens include

Answer 2

 The natural oestrogens include Estradiol, estrone and estriol which are more appropriate for HRT than
 Synthetic oestrogens (e.g. ethinylestradiol and mestranol).

Question 3

Tibolone

Answer 3

 Tibolone (combined HRT taken continuously) has estrogenic, progestogenic + weak androgenic activity

Question 4

Oestrogen therapy is given

Answer 4

 cyclically or continuously for many gynaecological conditions. If long-term therapy is required for women with a uterus, a progestogen should normally be added to reduce the risk of cystic hyperplasia of the endometrium… and possible transformation to cancer.

Question 5

Oestrogens are no longer used to

Answer 5

 supress lactation due to their association with thromboembolism.

Question 6

Vaginal atrophy treatment

Answer 6

 Vaginal atrophy is vaginal dryness. Treatment involves topical oestrogens, vaginal creams, tablets + rings

Question 7

Vasomotor symptoms and treatment

Answer 7

 Vasomotor symptoms inc hot flushes, night sweat  treat with systemic oestrogens, tablets or patches

Question 8

Choice of HRT

Answer 8

 Women without a uterus: Oestrogen alone continuously
 Women with a uterus: Oestrogen + Progestogen combined HRT cyclically or continuously (avoids withdrawal bleeding)
o Continuous combined HRT unsuitable in: Peri-menopause or <12 months since last period
o Rule out endometrial cancer if irregular bleeding continues after stopping continuous HRT

Question 9

For the treatment of menopausal symptoms, the benefits of

Answer 9

of short-term HRT outweigh the risks in women, especially those under 60 years.

Question 10

alleviating menopausal symptoms such as vaginal atrophy (thinning + drying of the vaginal walls due to less oestrogen) or vasomotor instability.

Answer 10

• HRT with small doses of an oestrogen (together with a progestogen in women with a uterus) is appropriate

Question 11

HRT is often given

Answer 11

• early in menopause (before the age of 45) until the age at which menopause should occur naturally, this reduces the risk of osteoporosis. Once older, alternative prophylaxis for osteoporosis should be used.

Question 12

However, HRT does increase the

Answer 12

• risk of VTE, stroke, endometrial cancer (reduced by a progestogen), breast cancer and ovarian cancer. There is also an increased risk of coronary heart disease in women who start combined HRT more than 10 years after menopause.

Question 13

The minimum effective dose of HRT should be used for

Answer 13

the shortest duration

Question 14

Contraception + HRT

Answer 14

• HRT does not provide contraception
 Under 50 years = fertile 2 years after last period (Use a low-oestrogen combined contraceptive) if free from venous/arterial disease risk factors
 Over 50 years = fertile 1 year after last period (Use barrier protection – condom)

Question 15

HRT and surgery

Answer 15

 Major surgery under general anaesthesia is a predisposing factor for VTE and may be necessary to stop HRT 4-6 weeks before surgery… it should be restarted only after full mobilisation.
 If HRT is continued or if discontinuation is not possible (e.g. in non-elective surgery)… prophylaxis with an unfractionated or LMWH and graduated compression hosiery is advised.

Question 16

Side effects of HRT:

Answer 16

 Cancer: Ovarian cancer, breast cancer, cervical cancer, endometrial cancer
 Coronary heart disease (If combined HRT started 10 years after menopause)

Question 17

Vasomotor symptoms  Clonidine may be used in

Answer 17

women cannot take an oestrogen, but Clonidine may cause unacceptable side effects

Question 18

Reasons to stop HRT

Answer 18

 Sudden, severe chest pain
 Sudden breathlessness (or cough with blood stained sputum)
 Unexplained swelling or severe pain in calf of one leg
 Severe stomach pain
 Serious neurological effects including unusual severe prolonged headache, sudden partial or complete loss of vision or sudden disturbance of hearing or other perceptual disorders. Dysphasia, slurred speech, bad fainting attack, collapse, first unexplained epileptic seizure, weakness, motor disturbances, very marked sudden numbness of one side or part of body
 Hepatitis, jaundice, liver enlargement
 Raised blood pressure (systolic >160mmHg or diastolic >95mmHg)
 Prolonged immobility after surgery or leg injury
 Detection of a risk factor which contraindicates treatment

Question 19

Risk factors that contraindicate HRT

Answer 19

 Prolonged immobility after surgery or leg injury (risk of VTE)
 Thrombophlebitis (inflammation of blood vessel walls)
 Angina, MI
 VTE
 Recurrent VTE (unless anticoagulated)
 Thrombophillic disorder (tendency to cause blood clots)
 Liver disease
 Untreated endometrial hyperplasia (endometrial cancer risk)
 Undiagnosed vaginal bleeding (endometrial cancer?)
 Oestrogen-dependent cancer
 History of breast cancer

Question 20

Progestogens

Answer 20

• Although oral progestogens have been used widely for menorrhagia, they are relatively ineffective compared with tranexamic acid.
• Oral progestogens have also been used for severe dysmenorrhoea, but where contraception is also required in younger women, the best choice is a combined oral contraceptive.
• Progestogens have been used for the prevention of miscarriages in women with a history of recurrent miscarriage, but there is no evidence of benefit and they are not recommended for this purpose.
• In women with a uterus, a progestogen needs to be added to long-term oestrogen therapy for hormone replacement, to prevent cystic hyperplasia and transformation to cancer.
• Desogestrel, Levonorgestrel, Gestodene, Norethisterone + Norgestimate are used in combined oral contraceptives and progestogen-only contraceptives.
• Progestogens also have a role in neoplastic disease

Question 21

Endometriosis

Answer 21

o A short trial (3 months) of paracetamol or NSAID alone is considered 1st line management of pain
o Hormonal treatment should be offered if diagnosis confirmed. Surgery is also an option

Question 22

Anti-oestrogens

Answer 22

• Clomifene (ovulation stimulant) -> used in infertility in women due to oligomenorrhoea, secondary amenorrhoea e.g. PCOS.
• Use for 6 cycles only due to increased risk of ovarian cancer.
• Side Effects: multiple pregnancies

Question 23

Menorrhagia

Answer 23

Heavy menstrual bleeding (Menorrhagia)

• > 80ml of blood lost for a duration of >7 days
• 1st line treatment: Levonorgestrel-releasing intra-uterine system
• 2nd Line: Tranexamic acid or NSAID or COC

Question 24

Male sex Hormones

Answer 24

Androgens cause masculinisation, they may be used as replacement therapy in castrated men or where they are hypogonadal due to pituitary or testicular disease. Intramuscular depot injections of Testosterone esters are preferred for replacement therapy

Question 25

Testosterone side effects:

Answer 25

Masculinisation –> virilisation in women, acne, male pattern baldness, sexual development in pre-pubescent males

Question 26

Anti-androgens

Answer 26

1. Cyproterone acetate

 Cyproterone acetate is an anti-androgen used in the treatment of severe hypersexuality and sexual deviation in the male. It inhibits spermatogenesis and produces reversible infertility (but is not a contraceptive), abnormal sperm forms are produced.

2. Finasteride and Dutasteride

 Finasteride and Dutasteride are useful for reducing prostate size in men with an enlarged prostate. They are alternatives to alpha-blockers.
 Finasteride is also licensed for use with Doxazosin in the management of benign prostatic hyperplasia
 A low strength of Finasteride is licensed for treating male-pattern baldness in men.

Question 27

Anabolic steroids

Answer 27

Anabolic steroids have some androgenic activity, but they cause less virilisation than androgens in women. They have been given for osteoporosis in women, but they are no longer recommended for this purpose. The protein-building properties of anabolic steroids have not proven beneficial in a clinical setting.
Monitor prostate + PSA in men over 45 years

Question 28

Virilisation is

Answer 28

development of male physical characteristics (e.g. body hair, deep voice)

Question 29

Male sex hormone antagonism

Answer 29

• Cyproterone (hepatotoxic)