children; compliance and skin irritation are sometimes a
problem.
Ethinylestradiol is occasionally used, underspecialist
supervision, for the management of hereditary
haemorrhagic telangiectasia (but evidence of benefitis
limited), for the prevention of tall stature, and in tests of
growth hormone secretion.
Topical oestrogen creams are used in the treatment of
labial adhesions.
Progestogens
There are two main groups of progestogen,progesterone and
its analogues(dydrogesterone and medroxyprogesterone
acetate) andtestosterone analogues(norethisterone p. 479
and norgestrel). The newer progestogens (desogestrel,
norgestimate, and gestodene) are all derivatives of
norgestrel; levonorgestrel is the active isomer of norgestrel
and has twice its potency. Progesterone and its analogues
are less androgenic than the testosterone derivatives and
neither progesterone nor dydrogesterone causes virilisation.
In delayed puberty cyclical progestogen is added after
12 – 18 months of oestrogen therapy to establish a menstrual
cycle.
Norethisterone is also used to postpone menstruation
during a cycle; treatment is started 3 days before the
expected onset of menstruation.7.1 Female sex hormone
responsive conditions
OESTROGENS
Ethinylestradiol
(Ethinyloestradiol)
lINDICATIONS AND DOSE
Induction of sexual maturation in girls
▶BY MOUTH
▶Child (female):Initially 2 micrograms daily for
6 months, then increased to 5 micrograms daily for
6 months, then increased to 10 micrograms daily for
6 months, then increased to 20 micrograms daily, after
12 – 18 months of treatment give progestogen for 7 days
of each 28 -day cycle.
Maintenance of sexual maturation in girls
▶BY MOUTH
▶Child (female): 20 micrograms daily, to be given with
cyclical progestogen for 7 days of each 28 -day cycle.
Prevention of tall stature in girls
▶BY MOUTH
▶Child 2–11 years (female): 20 – 50 micrograms daily.
Pituitary priming before growth hormone secretion test in
girls with bone age over 10 years
▶BY MOUTH
▶Child (female): 100 micrograms daily for 3 days before
test.lUNLICENSED USEUnlicensed for use in children.
lCONTRA-INDICATIONSAcute porphyrias p. 603.
cardiovascular disease (sodium retention with oedema).
family history of thromboembolism.gallstones.heart
disease associated with pulmonary hypertension.heart
disease associated with risk of embolus.history during
pregnancy of cholestatic jaundice.history during
pregnancy of chorea.history during pregnancy of
pemphigoid gestationis.history during pregnancy of
pruritus.history of breast cancer.history of haemolytic
uraemic syndrome.migraine with aura.sclerosing
treatment for varicose veins.severe or multiple riskfactors for arterial disease.severe or multiple risk factors
for venous thromboembolism.systemic lupus
erythematosus.transient cerebral ischaemic attacks
without headaches.undiagnosed vaginal bleeding.
venous thromboembolism, or history of recurrent venous
thromboembolism (unless already on anticoagulant
treatment)
lCAUTIONSActive trophoblastic disease (until return to
normal of urine- and plasma-gonadotrophin
concentration)—seek specialist advice.Crohn’s disease.
gene mutations associated with breast cancer (e.g. BRCA 1)
.history of severe depression (especially if induced by
hormonal contraceptive).hyperprolactinaemia (seek
specialist advice).inflammatory bowel disease.migraine
(migraine-like headaches).personal or family history of
hypertriglyceridaemia (increased risk of pancreatitis).risk
factors for arterial disease.risk factors for migraine.risk
factors for venous thromboembolism.sickle-cell disease.
undiagnosed breast mass
CAUTIONS, FURTHER INFORMATION
▶Other conditionsThe product literature advises caution in
other conditions including hypertension, renal disease,
asthma, epilepsy, sickle-cell disease, melanoma,
otosclerosis, multiple sclerosis, and systemic lupus
erythematosus (but care required if antiphospholipid
antibodies present, see above). Evidence for caution in
these conditions is unsatisfactory and many women with
these conditions may stand to benefit from treatment.
▶Risk of venous thromboembolismUse withcautionif any of
following factors present butavoidif two or more factors
present:
.family history of venous thromboembolisminfirst-degree
relative aged under 45 years (avoid if known
prothrombotic coagulation abnormality e.g. factor V
Leiden or antiphospholipid antibodies (including lupus
anticoagulant));
.obesity—body mass index 30 kg/m^2 (avoid if body mass
index 35 kg/m2
unless no suitable alternative); (In
adolescents, caution if obese according to BMI (adjusted
for age and gender); in those who are markedly obese,
avoid unless no suitable alternative);
.long-term immobilisatione.g. in a wheelchair (avoid if
confined to bed or leg in plaster cast);
.history of superficial thrombophlebitis;
.smoking.
▶Risk factors for arterial diseaseUse withcautionif any one of
following factors present butavoidif two or more factors
present:
.family history of arterial diseaseinfirst degree relative
aged under 45 years (avoid if atherogenic lipid profile);
.diabetes mellitus(avoid if diabetes complications
present);
.hypertension—blood pressure abovesystolic 140 mmHgor
diastolic 90 mmHg(avoid if blood pressure abovesystolic
160 mmHgordiastolic 95 mmHg); (In adolescents, avoid
if blood pressure very high);
.smoking(avoid if smoking 40 or more cigarettes daily);
.obesity(avoid if body mass index 35 kg/m^2 unless no
suitable alternative); (In adolescents, caution if obese
according to BMI (adjusted for age and gender); in those
who are markedly obese, avoid unless no suitable
alternative);
.migraine without aura(avoid ifmigraine with aura(focal
symptoms),orsevere migraine frequently lasting over
72 hours despite treatment,ormigraine treated with
ergot derivatives).
▶MigraineWomen should report any increase in headache
frequency or onset of focal symptoms (discontinue
immediately and refer urgently to neurology expert if focal
neurological symptoms not typical of aura persist for more
than 1 hour).478 Sex hormone responsive conditions BNFC 2018 – 2019
Endocrine system6