Sex hormone responsive conditions Flashcards
Oestrogens are necessary for
the development of female secondary sexual characteristics.
The natural and synthetic oestrogens include
The natural oestrogens include Estradiol, estrone and estriol which are more appropriate for HRT than
Synthetic oestrogens (e.g. ethinylestradiol and mestranol).
Tibolone
Tibolone (combined HRT taken continuously) has estrogenic, progestogenic + weak androgenic activity
Oestrogen therapy is given
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.
Oestrogens are no longer used to
supress lactation due to their association with thromboembolism.
Vaginal atrophy treatment
Vaginal atrophy is vaginal dryness. Treatment involves topical oestrogens, vaginal creams, tablets + rings
Vasomotor symptoms and treatment
Vasomotor symptoms inc hot flushes, night sweat treat with systemic oestrogens, tablets or patches
Choice of HRT
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
For the treatment of menopausal symptoms, the benefits of
of short-term HRT outweigh the risks in women, especially those under 60 years.
alleviating menopausal symptoms such as vaginal atrophy (thinning + drying of the vaginal walls due to less oestrogen) or vasomotor instability.
• HRT with small doses of an oestrogen (together with a progestogen in women with a uterus) is appropriate
HRT is often given
• 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.
However, HRT does increase the
• 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.
The minimum effective dose of HRT should be used for
the shortest duration
Contraception + HRT
• 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)
HRT and surgery
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.
Side effects of HRT:
Cancer: Ovarian cancer, breast cancer, cervical cancer, endometrial cancer
Coronary heart disease (If combined HRT started 10 years after menopause)
Vasomotor symptoms Clonidine may be used in
women cannot take an oestrogen, but Clonidine may cause unacceptable side effects
Reasons to stop HRT
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
Risk factors that contraindicate HRT
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
Progestogens
- 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
Endometriosis
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
Anti-oestrogens
- 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
Menorrhagia
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
Male sex Hormones
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
