required before treatment initiation—consult product
literature). diabetes mellitus (adjustment of antidiabetic
▶ Frequency not known Anger. angioedema . hepatic
function abnormal . laryngospasm
SIDE-EFFECTS, FURTHER INFORMATION Injection-site
reactions Rotate injection sites to avoid lipohypertrophy.
Abnormal hepatic function Manufacturer advises
interrupt treatment if liver function tests at least 5 times
the upper limit of normal or transaminase levels at least
3 times the upper limit of normal and blood bilirubin
increased—consult product literature. Discontinue if liver
l CONCEPTION AND CONTRACEPTION Possible increase in
l HEPATIC IMPAIRMENT Manufacturer advises caution (no
information available); temporary or permanent
withdrawal may be needed—consult product literature.
▶ Manufacturer advises assess liver function tests before
treatment initiation and monitor liver function tests
during treatment—consult product literature.
▶ Manufacturer advises monitor serum IGF-I
l NATIONAL FUNDING/ACCESS DECISIONS
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (November
2017) that pegvisomant (Somavert ®) is accepted for use
within NHS Scotland for the treatment of patients with
acromegaly who have had an inadequate response to
surgery and/or radiation therapy and in whom an
appropriate medical treatment with somatostatin
analogues did not normalise IGF-1 [insulin-like growth
factor 1] concentrations or was not tolerated. This advice is
contingent upon the continuing availability of the patient
access scheme in NHS Scotland or a list price that is
All Wales Medicines Strategy Group (AWMSG) decisions
The All Wales Medicines Strategy Group has advised
(November 2017) that pegvisomant (Somavert ®) is
recommended as an option for use within NHS Wales for
the treatment of patients with acromegaly who have had
an inadequate response to surgery and/or radiation
therapy and in whom an appropriate medical treatment
tolerated. This recommendation applies only in
circumstances where the approved Wales Patient Access
Scheme (WPAS) is utilised or where the list/contract price
is equivalent or lower than the WPAS price.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder and solvent for solution for injection
Pegvisomant 10 mg Somavert 10mg powder and solvent for solution
for injection vials | 30 vial P £1,500.00 (Hospital only)
Pegvisomant 15 mg Somavert 15mg powder and solvent for solution
for injection vials | 30 vial P £2,250.00 (Hospital only)
Pegvisomant 20 mg Somavert 20mg powder and solvent for solution
for injection vials | 1 vial P £100.00 (Hospital only) | 30 vial P £3,000.00 (Hospital only)
Pegvisomant 25 mg Somavert 25mg powder and solvent for solution
for injection vials | 30 vial P £3,750.00 (Hospital only)
Pegvisomant 30 mg Somavert 30mg powder and solvent for solution
for injection vials | 30 vial P £4,500.00 (Hospital only)
PITUITARY AND HYPOTHALAMIC HORMONES
AND ANALOGUES › HUMAN GROWTH HORMONES
(Recombinant Human Growth Hormone)
Gonadal dysgenesis (Turner syndrome)
▶ Adult: 1.4 mg/m2 daily, alternatively
▶ Adult: Initially 150–300 micrograms daily, then
increased if necessary up to 1 mg daily, dose to be
increased gradually, use minimum effective dose
(requirements may decrease with age)
DOSE EQUIVALENCE AND CONVERSION
▶ Dose formerly expressed in units; somatropin 1 mg :
l CONTRA-INDICATIONS Evidence of tumour activity
(complete antitumour therapy and ensure intracranial
lesions inactive before starting). not to be used after renal
l CAUTIONS Diabetes mellitus (adjustment of antidiabetic
therapy may be necessary). disorders of the epiphysis of
thyroid function tests but limited evidence of clinical value
. initiation of treatment close to puberty not
recommended in child born small for corrected gestational
age . papilloedema .relative deficiencies of other pituitary
hormones .resolved intracranial hypertension (monitor
closely). Silver-Russell syndrome
l INTERACTIONS → Appendix 1: somatropin
▶ Common or very common Carpal tunnel syndrome . fluid
retention . headache . joint disorders . lipoatrophy . myalgia . oedema . paraesthesia
▶ Uncommon Gynaecomastia . idiopathic intracranial
▶ Frequency not known Leukaemia . musculoskeletal
SIDE-EFFECTS, FURTHER INFORMATION Funduscopy for
papilloedema recommended if severe or recurrent
headache, visual problems, nausea and vomiting occur—if
papilloedema confirmed consider benign intracranial
hypertension (rare cases reported).
748 Hypothalamic and anterior pituitary hormone related disorders BNF 78
l PREGNANCY Discontinue if pregnancy occurs—no
l BREAST FEEDING No information available. Absorption
l DIRECTIONS FOR ADMINISTRATION Rotate subcutaneous
injection sites to prevent lipoatrophy.
SAIZEN ® SOLUTION FOR INJECTION For use by
NORDITROPIN ® PREPARATIONS For use by subcutaneous
OMNITROPE ® For use by subcutaneous injection.
NUTROPINAQ ® For use by subcutaneous injection.
HUMATROPE ® Cartridges for use by subcutaneous
Powder for reconstitution for use by subcutaneous or
ZOMACTON ® For use by subcutaneous injection.
SAIZEN ® POWDER AND SOLVENT FOR SOLUTION FOR
INJECTION For use by subcutaneous injection.
GENOTROPIN ® PREPARATIONS For use by subcutaneous
l PRESCRIBING AND DISPENSING INFORMATION Somatropin
is a biological medicine. Biological medicines must be
prescribed and dispensed by brand name, see Biological
medicines and Biosimilar medicines, under Guidance on
SAIZEN ® SOLUTION FOR INJECTION For use with
cool.click ® needle-free autoinjector device or easypod ®
autoinjector device (non-NHS but available free of charge
NORDITROPIN ® PREPARATIONS Cartridges are for use with
appropriate NordiPen ® device (non-NHS but available free
Multidose disposable prefilled pens for use with
NovoFine ® or NovoTwist ® needles.
OMNITROPE ® For use with Omnitrope Pen 5 ® and
Omnitrope Pen 10 ® devices (non-NHS but available free of
NUTROPINAQ ® For use with NutropinAq ® Pen device
(non-NHS but available free of charge from clinics).
ZOMACTON ® 4 mg vial for use with ZomaJet 2 ® Vision
needle-free device (non-NHS but available free of charge
from clinics) or with needles and syringes.
10 mg vial for use with ZomaJet Vision X ® needle-free
device (non-NHS but available free of charge from clinics)
SAIZEN ® POWDER AND SOLVENT FOR SOLUTION FOR
INJECTION For use with one. click ® autoinjector device or
cool.click ® needle-free autoinjector device or easypod ®
autoinjector device (non-NHS but available free of charge
GENOTROPIN ® PREPARATIONS Cartridges are for use with
Genotropin ® Pen device (non-NHS but available free of
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Somatropin for the treatment of growth failure in children
Somatropin is recommended for children with growth
. have growth-hormone deficiency
. have chronic renal insufficiency
. are born small for gestational age with subsequent
growth failure at 4 years of age or later
. have short stature homeobox-containing gene (SHOX)
Treatment should be discontinued if growth velocity
increases by less than 50% from baseline in the first year of
▶ Somatropin for adults with growth hormone deficiency
Somatropin is recommended in adults only if the
following 3 criteria are fulfilled:
. Severe growth hormone deficiency, established by an
. Impaired quality of life, measured by means of a specific
. Already receiving treatment for another pituitary
Somatropin treatment should be discontinued if the
quality of life has not improved sufficiently by 9 months.
Severe growth hormone deficiency developing after
linear growth is complete but before the age of 25 years
should be treated with growth hormone; treatment should
continue until adult peak bone mass has been achieved.
Treatment for adult-onset growth hormone deficiency
should be stopped only when the patient and the patient’s
physician consider it appropriate.
Treatment with somatropin should be initiated and
managed by a physician with expertise in growth hormone
disorders; maintenance treatment can be prescribed in the
community under a shared-care protocol.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
EXCIPIENTS: May contain Benzyl alcohol
▶ Norditropin NordiFlex (Novo Nordisk Ltd)
Somatropin (epr) 3.3 mg per 1 ml Norditropin NordiFlex 5mg/1.5ml
solution for injection pre-filled pen | 1 pre-filled disposable
Somatropin (epr) 6.7 mg per 1 ml
injection P £115.90 DT = £115.90
10mg/1.5ml solution for injection pre-filled pen | 1 pre-filled
Somatropin (epr) 10 mg per 1 ml
disposable injection P £231.80 DT = £
15mg/1.5ml solution for injection pre-filled pen | 1 pre-filled
Somatropin (epr) 3.3 mg per 1 ml Norditropin SimpleXx 5mg/1.5ml
solution for injection cartridges | 1 cartridge P £106.35 DT =
Somatropin (epr) 6.7 mg per 1 ml
10mg/1.5ml solution for injection cartridges | 1 cartridge P £
Somatropin (epr) 10 mg per 1 ml
Norditropin SimpleXx 15mg/1.5ml
solution for injection cartridges | 1 cartridge P £319.05 DT =
Somatropin (rbe) 5 mg per 1 ml NutropinAq 10mg/2ml solution for
▶ Omnitrope SurePal (Sandoz Ltd)
Somatropin (rbe) 3.333 mg per 1 ml Omnitrope SurePal 5
5mg/1.5ml solution for injection cartridges | 5 cartridge P £
Somatropin (rbe) 6.667 mg per 1 ml
10mg/1.5ml solution for injection cartridges | 5 cartridge P £
Somatropin (rbe) 10 mg per 1 ml
15mg/1.5ml solution for injection cartridges | 5 cartridge P
Somatropin (rmc) 5.825 mg per 1 ml Saizen 6mg/1.03ml solution
for injection cartridges | 1 cartridge P £139.08 DT =
Somatropin (rmc) 8 mg per 1 ml
£139.08e Saizen 12mg/1.5ml solution for
20mg/2.5ml solution for injection cartridges
| 1 cartridge P £278.16 DT = £
1 cartridge P £463.60 DT = £463.60e
BNF 78 Growth hormone disorders 749
Powder and solvent for solution for injection
EXCIPIENTS: May contain Benzyl alcohol
Somatropin (rbe) 5.3 mg Genotropin 5.3mg powder and solvent for
solution for injection cartridges | 1 cartridge P £92.15 DT =
Genotropin 12mg powder and solvent for
solution for injection cartridges | 1 cartridge P £208.65 DT =
Somatropin (rbe) 5.3 mg Genotropin GoQuick 5.3mg powder and
solvent for solution for injection pre-filled pen | 1 pre-filled disposable
solvent for solution for injection pre-filled pen | 1 pre-filled disposable
Somatropin (rbe) 200 microgram Genotropin MiniQuick
200microgram powder and solvent for solution for injection pre-filled
disposable devices | 7 pre-filled disposable injection P £24.35 DT
Somatropin (rbe) 400 microgram
400microgram powder and solvent for solution for injection pre-filled
disposable devices | 7 pre-filled disposable injection P £48.68 DT
Somatropin (rbe) 600 microgram
600microgram powder and solvent for solution for injection pre-filled
disposable devices | 7 pre-filled disposable injection P £73.03 DT
Somatropin (rbe) 800 microgram
800microgram powder and solvent for solution for injection pre-filled
disposable devices | 7 pre-filled disposable injection P £97.37 DT
Genotropin MiniQuick 1mg powder and
solvent for solution for injection pre-filled disposable devices | 7 preSomatropin (rbe) 1.2 mg
solvent for solution for injection pre-filled disposable devices | 7 preSomatropin (rbe) 1.4 mg
solvent for solution for injection pre-filled disposable devices | 7 preSomatropin (rbe) 1.6 mg
solvent for solution for injection pre-filled disposable devices | 7 preSomatropin (rbe) 1.8 mg
solvent for solution for injection pre-filled disposable devices | 7 preSomatropin (rbe) 2 mg
solvent for solution for injection pre-filled disposable devices | 7 pre-
Somatropin (rbe) 6 mg Humatrope 6mg powder and solvent for
solution for injection cartridges | 1 cartridge P £108.00 DT =
Humatrope 12mg powder and solvent for
solution for injection cartridges | 1 cartridge P £216.00 DT =
Humatrope 24mg powder and solvent for
solution for injection cartridges | 1 cartridge P £432.00 DT =
Somatropin (rmc) 8 mg Saizen 8mg click.easy powder and solvent
for solution for injection vials | 1 vial P £185.44 DT =
Somatropin (rbe) 4 mg Zomacton 4mg powder and solvent for
solution for injection vials |
1 vial P10mg powder and solvent for
solution for injection vials | 1 vial P £170.70 DT = £170.70e
Oestrogens are necessary for the development of female
secondary sexual characteristics; they also stimulate
myometrial hypertrophy with endometrial hyperplasia.
In terms of oestrogenic activity natural oestrogens
(estradiol p. 756 (oestradiol), estrone (oestrone), and estriol
p. 832 (oestriol)) have a more appropriate profile for
hormone replacement therapy (HRT) than synthetic
oestrogens (ethinylestradiol p. 759 (ethinyloestradiol) and
mestranol). Tibolone p. 760 has oestrogenic, progestogenic
Oestrogen therapy is given cyclically or continuously for a
number of gynaecological conditions. If long-term therapy is
required in women with a uterus, a progestogen should
normally be added to reduce the risk of cystic hyperplasia of
the endometrium (or of endometriotic foci in women who
have had a hysterectomy) and possible transformation to
Oestrogens are no longer used to suppress lactation
because of their association with thromboembolism.
Hormone replacement therapy (HRT) with small doses of an
oestrogen (together with a progestogen in women with a
uterus) is appropriate for alleviating menopausal symptoms
such as vaginal atrophy or vasomotor instability. Oestrogen
given systemically in the perimenopausal and
postmenopausal period or tibolone given in the
postmenopausal period also diminish postmenopausal
osteoporosis but other drugs are preferred. Menopausal
atrophic vaginitis may respond to a short course of a topical
vaginal oestrogen preparation used for a few weeks and
Systemic therapy with an oestrogen or drugs with
oestrogenic properties alleviates the symptoms of oestrogen
deficiency such as vasomotor symptoms. Tibolone combines
oestrogenic and progestogenic activity with weak androgenic
activity; it is given continuously, without cyclical
HRT may be used in women with early natural or surgical
menopause (before age 45 years), since they are at high risk
of osteoporosis. For early menopause, HRT can be given
until the approximate age of natural menopause (i.e. until
age 50 years). Alternatives to HRT should be considered if
osteoporosis is the main concern.
Clonidine hydrochloride p. 145 may be used to reduce
vasomotor symptoms in women who cannot take an
oestrogen, but clonidine hydrochloride may cause
HRT increases the risk of venous thromboembolism,
stroke, endometrial cancer (reduced by a progestogen),
breast cancer, and ovarian cancer; there is an increased risk
of coronary heart disease in women who start combined HRT
more than 10 years after menopause. For details of these
The minimum effective dose of HRT should be used for the
shortest duration. Treatment should be reviewed at least
annually and for osteoporosis alternative treatments
considered. HRT does not prevent coronary heart disease or
protect against a decline in cognitive function and it should
not be prescribed for these purposes. Experience of treating
women over 65 years with HRT is limited.
750 Sex hormone responsive conditions BNF 78
For the treatment of menopausal symptoms the benefits of
short-term HRT outweigh the risks in the majority of
women, especially in those aged under 60 years.
For the treatment of menopausal symptoms in women
with breast cancer see Breast cancer p. 942.
It is estimated that using all types of HRT, including
tibolone, increases the risk of breast cancer within 1–2 years
of initiating treatment. The increased risk is related to the
duration of HRT use (but not to the age at which HRT is
started) and this excess risk disappears within 5 years of
stopping. Radiological detection of breast cancer can be
made more difficult as mammographic density can increase
with HRT use; tibolone has only a limited effect on
The increased risk of endometrial cancer depends on the
dose and duration of oestrogen-only HRT. In women with a
uterus, the addition of a progestogen cyclically (for at least
10 days per 28-day cycle) reduces the additional risk of
endometrial cancer; this additional risk is eliminated if a
progestogen is given continuously. However, this should be
weighed against the increased risk of breast cancer.
Long-term use of combined HRT or oestrogen-only HRT is
associated with a small increased risk of ovarian cancer; this
excess risk disappears within a few years of stopping.
Risk of venous thromboembolism
Women using combined or oestrogen-only HRT are at an
increased risk of deep vein thrombosis and of pulmonary
embolism especially in the first year of use. In women who
have predisposing factors (such as a personal or family
history of deep vein thrombosis or pulmonary embolism,
cases the risks of HRT may exceed the benefits. Travel
involving prolonged immobility further increases the risk of
Risk of stroke increases with age, therefore older women
have a greater absolute risk of stroke. Combined HRT or
oestrogen-only HRT slightly increases the risk of stroke.
Tibolone increases the risk of stroke about 2.2 times from the
Risk of coronary heart disease
HRT does not prevent coronary heart disease and should not
be prescribed for this purpose. There is an increased risk of
coronary heart disease in women who start combined HRT
more than 10 years after menopause. Although very little
information is available on the risk of coronary heart disease
in younger women who start HRT close to the menopause,
studies suggest a lower relative risk compared with older
The choice of HRT for an individual depends on an overall
balance of indication, risk, and convenience. A woman with a
uterus normally requires oestrogen with cyclical progestogen
for the last 12 to 14 days of the cycle or a preparation which
involves continuous administration of an oestrogen and a
progestogen (or one which provides both oestrogenic and
progestogenic activity in a single preparation). Continuous
combined preparations or tibolone are not suitable for use
in the perimenopause or within 12 months of the last
menstrual period; women who use such preparations may
bleed irregularly in the early stages of treatment—if bleeding
continues endometrial abnormality should be ruled out and
consideration given to changing to cyclical HRT.
An oestrogen alone is suitable for continuous use in
women without a uterus. However, in endometriosis,
endometrial foci may remain despite hysterectomy and the
addition of a progestogen should be considered in these
An oestrogen may be given by mouth or by transdermal
administration, which avoids first-pass metabolism.
Major surgery under general anaesthesia, including
orthopaedic and vascular leg surgery, is a predisposing factor
for venous thromboembolism and it may be prudent 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 unfractionated or low molecular weight
heparin and graduated compression hosiery is advised.
Hormone replacement therapy should be stopped (pending
investigation and treatment), if any of the following occur:
. sudden severe chest pain (even if not radiating to left
. sudden breathlessness (or cough with blood-stained
. unexplained swelling or severe pain in calf of one leg;
. serious neurological effects including unusual severe,
prolonged headache especially if first time or getting
progressively worse or sudden partial or complete loss of
vision or sudden disturbance of hearing or other
perceptual disorders or dysphasia or bad fainting attack or
collapse or first unexplained epileptic seizure or weakness,
motor disturbances, very marked numbness suddenly
affecting one side or one part of body;
. hepatitis, jaundice, liver enlargement;
. blood pressure above systolic 160 mmHg or diastolic
. prolonged immobility after surgery or leg injury;
. detection of a risk factor which contra-indicates treatment
Ethinylestradiol p. 759 (ethinyloestradiol) is licensed for
short-term treatment of symptoms of oestrogen deficiency,
for osteoporosis prophylaxis if other drugs cannot be used
and for the treatment of female hypogonadism and
Ethinylestradiol is occasionally used under specialist
supervision for the management of hereditary haemorrhagic
telangiectasia (but evidence of benefit is limited). It is also
used licensed for the palliative treatment of prostate cancer.
Raloxifene hydrochloride p. 754 is licensed for the treatment
and prevention of postmenopausal osteoporosis; unlike
hormone replacement therapy, raloxifene hydrochloride
does not reduce menopausal vasomotor symptoms.
Progestogens and progesterone receptor
There are two main groups of progestogen, progesterone and
its analogues (dydrogesterone and medroxyprogesterone
acetate p. 810) and testosterone analogues (norethisterone
p. 764 and norgestrel). The newer progestogens (desogestrel
p. 805, norgestimate, and gestodene) are all derivatives of
norgestrel; levonorgestrel p. 806 is the active isomer of
norgestrel and has twice its potency. Progesterone p. 765
and its analogues are less androgenic than the testosterone
derivatives and neither progesterone nor dydrogesterone
Where endometriosis requires drug treatment, it may
respond to a progestogen, e.g. norethisterone, administered
on a continuous basis. Danazol p. 742 and gonadorelin
Although oral progestogens have been used widely for
menorrhagia (see Heavy menstrual bleeding p. 753) they are
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