There can be variation in the licensing of
different medicines containing the same drug.
Solution for injection
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 pens | 1 pre-filled disposable
injection P £115.90 DT = £115.90 e
Somatropin (epr) 6.7 mg per 1 ml Norditropin NordiFlex
10mg/1.5ml solution for injection pre-filled pens | 1 pre-filled
disposable injection P £231.80 DT = £231.80 e
Somatropin (epr) 10 mg per 1 ml Norditropin NordiFlex
15mg/1.5ml solution for injection pre-filled pens | 1 pre-filled
disposable injection P £347.70 DT = £347.70 e
▶Norditropin SimpleXx (Novo Nordisk Ltd)
Somatropin (epr) 3.3 mg per 1 ml Norditropin SimpleXx 5mg/1.5ml
solution for injection cartridges | 1 cartridge P £106.35 DT =
£106.35 e
Somatropin (epr) 6.7 mg per 1 ml Norditropin SimpleXx
10mg/1.5ml solution for injection cartridges | 1 cartridge P
£212.70 DT = £212.70 e
Somatropin (epr) 10 mg per 1 ml Norditropin SimpleXx 15mg/1.5ml
solution for injection cartridges | 1 cartridge P £319.05 DT =
£319.05 e
▶NutropinAq (Ipsen Ltd)
Somatropin (rbe) 5 mg per 1 ml NutropinAq 10mg/2ml solution for
injection cartridges | 1 cartridge P £203.00 DT = £203.00 e
| 3 cartridge P £609.00 DT = £609.00 e
▶Omnitrope (Sandoz Ltd)
Somatropin (rbe) 3.333 mg per 1 ml Omnitrope Pen 5 5mg/1.5ml
solution for injection cartridges | 5 cartridge P £368.74 DT =
£368.74 e
Endocrine system
▶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
£368.74 DT = £368.74 e
Somatropin (rbe) 6.667 mg per 1 ml Omnitrope SurePal 10
10mg/1.5ml solution for injection cartridges | 5 cartridge P
£737.49 DT = £737.49 e
Somatropin (rbe) 10 mg per 1 ml Omnitrope SurePal 15
15mg/1.5ml solution for injection cartridges | 5 cartridge P
£1,106.22 DT = £1,106.22 e
▶Saizen (Merck Serono Ltd)
Somatropin (rmc) 5.825 mg per 1 ml Saizen 6mg/1.03ml solution
for injection cartridges | 1 cartridge P £139.08 DT =
£139.08 e
Somatropin (rmc) 8 mg per 1 ml Saizen 12mg/1.5ml solution for
injection cartridges | 1 cartridge P £278.16 DT = £278.16 e
Saizen 20mg/2.5ml solution for injection cartridges |
1 cartridge P £463.60 DT = £463.60 e
Powder and solvent for solution for injection
EXCIPIENTS: May contain Benzyl alcohol
▶Genotropin (Pfizer Ltd)
Somatropin (rbe) 5.3 mg Genotropin 5.3mg powder and solvent for
solution for injection cartridges | 1 cartridge P £92.15 DT =
£92.15 e
Somatropin (rbe) 12 mg Genotropin 12mg powder and solvent for
solution for injection cartridges | 1 cartridge P £208.65 DT =
£208.65 e
▶Genotropin GoQuick (Pfizer Ltd)
Somatropin (rbe) 5.3 mg Genotropin GoQuick 5.3mg powder and
solvent for solution for injection pre-filled pens | 1 pre-filled
disposable injection P £92.15 DT = £92.15 e
Somatropin (rbe) 12 mg Genotropin GoQuick 12mg powder and
solvent for solution for injection pre-filled pens | 1 pre-filled
disposable injection P £208.65 DT = £208.65 e
▶Genotropin MiniQuick (Pfizer Ltd)
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
= £24.35 e
Somatropin (rbe) 400 microgram Genotropin MiniQuick
400microgram powder and solvent for solution for injection pre-filled
disposable devices | 7 pre-filled disposable injection P £48.68 DT
= £48.68 e
Somatropin (rbe) 600 microgram Genotropin MiniQuick
600microgram powder and solvent for solution for injection pre-filled
disposable devices | 7 pre-filled disposable injection P £73.03 DT
= £73.03 e
Somatropin (rbe) 800 microgram Genotropin MiniQuick
800microgram powder and solvent for solution for injection pre-filled
disposable devices | 7 pre-filled disposable injection P £97.37 DT
= £97.37 e
Somatropin (rbe) 1 mg Genotropin MiniQuick 1mg powder and
solvent for solution for injection pre-filled disposable devices | 7 pre-
filled disposable injection P £121.71 DT = £121.71 e
Somatropin (rbe) 1.2 mg Genotropin MiniQuick 1.2mg powder and
solvent for solution for injection pre-filled disposable devices | 7 pre-
filled disposable injection P £146.06 DT = £146.06 e
Somatropin (rbe) 1.4 mg Genotropin MiniQuick 1.4mg powder and
solvent for solution for injection pre-filled disposable devices | 7 pre-
filled disposable injection P £170.39 DT = £170.39 e
Somatropin (rbe) 1.6 mg Genotropin MiniQuick 1.6mg powder and
solvent for solution for injection pre-filled disposable devices | 7 pre-
filled disposable injection P £194.74 DT = £194.74 e
Somatropin (rbe) 1.8 mg Genotropin MiniQuick 1.8mg powder and
solvent for solution for injection pre-filled disposable devices | 7 pre-
filled disposable injection P £219.08 DT = £219.08 e
Somatropin (rbe) 2 mg Genotropin MiniQuick 2mg powder and
solvent for solution for injection pre-filled disposable devices | 7 pre-
filled disposable injection P £243.42 DT = £243.42 e
▶Humatrope (Eli Lilly and Company Ltd)
Somatropin (rbe) 6 mg Humatrope 6mg powder and solvent for
solution for injection cartridges | 1 cartridge P £108.00 DT =
£108.00 e
Somatropin (rbe) 12 mg Humatrope 12mg powder and solvent for
solution for injection cartridges | 1 cartridge P £216.00 DT =
£208.65 e
Somatropin (rbe) 24 mg Humatrope 24mg powder and solvent for
solution for injection cartridges | 1 cartridge P £432.00 DT =
£432.00 e
▶Saizen (Merck Serono Ltd)
Somatropin (rmc) 8 mg Saizen 8mg click.easy powder and solvent
for solution for injection vials | 1 vial P £185.44 DT =
£185.44 e
▶Zomacton (Ferring Pharmaceuticals Ltd)
Somatropin (rbe) 4 mg Zomacton 4mg powder and solvent for
solution for injection vials | 1 vial P £68.28 DT = £68.28 e
Somatropin (rbe) 10 mg Zomacton 10mg powder and solvent for
solution for injection vials | 1 vial P £170.70 DT = £170.70 e
Sex hormone responsive
conditions
Sex hormones
Oestrogens and HRT
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. 799 (oestradiol), estrone (oestrone), and estriol
p. 877 (oestriol)) have a more appropriate profile for
hormone replacement therapy (HRT) than synthetic
oestrogens (ethinylestradiol p. 802 (ethinyloestradiol) and
mestranol). Tibolone p. 803 has oestrogenic, progestogenic
and weak androgenic activity.
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
cancer.
Oestrogens are no longer used to suppress lactation
because of their association with thromboembolism.
Hormone replacement therapy
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
repeated if necessary.
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
progestogen.
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. 156 may be used to reduce
vasomotor symptoms in women who cannot take an
oestrogen, but clonidine hydrochloride may cause
unacceptable side-effects.
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
risks see HRT Risk table.
The Medicines and Healthcare products Regulatory
Agency (MHRA) advises that HRT should only be prescribed
to relieve post-menopausal symptoms that are adversely
affecting quality of life and treatment should be reviewed
regularly to ensure the minimum effective dose is used for
the shortest duration. For osteoporosis, consider alternative
treatments. 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.
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. 994.
Risk of breast cancer
All types of systemic (oral or transdermal) HRT treatment
increase the risk of breast cancer after 1 year of use. This risk
is higher for combined oestrogen-progestogen HRT
(particularly for continuous HRT preparations where both
oestrogen and progestogen are taken throughout each
month) than for oestrogen-only HRT, but is irrespective of
the type of oestrogen or progestogen. Longer duration of
HRT use (but not the age at which HRT is started) further
increases risk.
Although the risk of breast cancer is lower after stopping
HRT than it is during current use, the excess risk persists for
more than 10 years after stopping compared with women
who have never used HRT. Vaginal preparations containing
low doses of oestrogen to treat local symptoms are not
thought to be associated with an effect on breast cancer risk.
The MHRA advises discussing the updated information on
the risk of breast cancer with women who use or are
considering starting HRT, at their next routine appointment.
The MHRA advises encouraging current and past HRT users
to be vigilant for signs of breast cancer and to attend routine
breast screening. If a decision is made to stop treatment, in
the absence of contra-indications, the MHRA recommends
this should be done gradually to minimise recurrence of
menopausal symptoms. For more information, see estradiol
p. 799, conjugated oestrogens (equine) p. 797 and the MHRA
Drug Safety Update: www.gov.uk/drug-safety-update/hormone-
replacement-therapy-hrt-further-information-on-the-known-
increased-risk-of-breast-cancer-with-hrt-and-its-persistence-after-
stopping.
Radiological detection of breast cancer can be made more
difficult as mammographic density can increase with HRT
use especially oestrogen-progestogen combined treatment,
but this is not thought to be the case with tibolone p. 803.
Tibolone p. 803 has also been associated with an increased
risk of breast cancer during treatment, although the extent
of risk and its persistence after stopping is currently
inconclusive.
Risk of endometrial cancer
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.
The risk of endometrial cancer in women who have not used
HRT increases with body mass index (BMI); the increased
risk of endometrial cancer in users of oestrogen-only HRT or
tibolone is more apparent in women who are not overweight.
Evidence suggests an increased risk of endometrial cancer
with tibolone. After 2.7 years of use (in women of average
age 68 years), 1 extra case of endometrial hyperplasia and 4
extra cases of endometrial cancer were diagnosed compared
with placebo users.
Risk of ovarian cancer
Endocrine system
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,
severe varicose veins, obesity, trauma, or prolonged bed-
rest) it is prudent to review the need for HRT, as in some
cases the risks of HRT may exceed the benefits. Travel
involving prolonged immobility further increases the risk of
deep vein thrombosis.
Although the level of risk of thromboembolism associated
with non-oral routes of administration of HRT has not been
established, it may be lower for the transdermal route.
Limited data does not suggest an increased risk of
thromboembolism with tibolone compared with combined
HRT or women not taking HRT.
Risk of stroke
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 first year of treatment; risk of stroke is age-dependent
and therefore the absolute risk of stroke with tibolone
increases with age.
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
women.
There is insufficient data to draw a conclusion on the risk
of coronary heart disease with tibolone.
Choice
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 p. 803 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
circumstances.
An oestrogen may be given by mouth or by transdermal
administration, which avoids first-pass metabolism.
Considerations in the elderly
The use of oestrogens in elderly patients is potentially
inappropriate (STOPP criteria) if prescribed in patients with
a history of breast cancer or venous thromboembolism
(increased risk of recurrence). Oral oestrogens may be
inappropriate if prescribed without concurrent progestogen
in those with an intact uterus (risk of endometrial cancer).
For further information, see STOPP/START criteria in
Prescribing in the elderly p. 33.
Endocrine system
Table1:SummaryofHRTrisksandbenefits*duringcurrentuseandcurrentusepluspostͲtreatmentfrom
ageofmenopauseuptoage69years,per1000womenwith5yearsor10yearsuseofHRT
Risksover5yearsuse
Totalrisksuptoage69
(withnouseor5years
(afternouseorafter
5yearsHRTuse†)
currentHRTuse)
Casesper
Extracases
Casesper
1000
per1000
1000
women
women
women
usingHRT
withno
withno
HRTuse
HRTuse
RisksassociatedwithcombinedestrogenͲprogestogenHRT
Breastcancer
13
+8
63
SequentialHRT
13
63
+7
ContinuouscombinedHRT
13
63
+10
Endometrialcancer
2
10
Ͳ
Ovariancancer
2
10
+<1
5
26
Venousthromboembolism
+7
(VTE)§
Stroke
4
26
+1
14
88
Coronaryheartdisease
Ͳ
(CHD)
Fractureoffemur
1.5
12
Ͳ
RisksassociatedwithestrogenͲonlyHRT
Breastcancer
13
+3
63
Endometrialcancer
2
+4
10
Ovariancancer
2
10
+<1
5
26
Venousthromboembolism
+2
(VTE)§
Stroke
4
26
+1
14
88
Coronaryheartdisease
Ͳ
(CHD)
Fractureoffemur
0.5
12
Ͳ
*Menopausalsymptomreliefisnotincludedinthistable,butisakeybenefitofHRTandwillplayamajorpartinthedecisiontoprescribeHRT.
†BestestimatesbasedonrelativerisksofHRTusefromage50(seeDSUtable2forrelativerisks).Forbreastcancerthisincludescasesdiagnosedduringcurrent
HRTuseanddiagnosedafterHRTuseuntilage69years;forotherrisks,thisassumesnoresidualeffectsafterstoppingHRTuse.
§LatestevidencesuggeststhattransdermalHRTproductshavealowerriskofVTEthanoralpreparations.
ZĞƉƌŽĚƵĐĞĚǁŝƚŚƉĞƌŵŝƐƐŝŽŶŽĨƚŚĞD,ZƵŶĚĞƌƚŚĞƚĞƌŵƐŽĨƚŚĞKƉĞŶ'ŽǀĞƌŶŵĞŶƚ>ŝĐĞŶĐĞ;K'>Ϳǀϯ͘Ϭ
Surgery
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.
Risksover10years
Totalrisksuptoage
(withnouseor10
69
yearscurrentHRTuse)
(afternouseorafter
10yearsHRTuse†)
Extra
Casesper
Extra
Casesper
Extra
cases
1000
cases
1000
cases
per1000
women
per1000
women
per1000
women
withno
women
withno
women
HRTuse
HRTuse
using
using
using
HRT
HRT
HRT
+17
27
+20
63
+34
27
63
+14
+17
+29
27
63
+20
+25
+40
4
10
Ͳ
Ͳ
Ͳ
4
10
+<1
+1
+1
8
26
+7
+13
+13
8
26
+1
+2
+2
28
88
Ͳ
Ͳ
Ͳ
1
12
Ͳ
Ͳ
Ͳ
+5
27
+7
63
+11
+4
4
+32
10
+32
4
10
+<1
+1
+1
10
26
+2
+3
+3
8
26
+1
+2
+2
28
88
Ͳ
Ͳ
Ͳ
1
12
Ͳ
Ͳ
Ͳ
Table2:Detailedsummaryofrelativeandabsoluterisksandbenefitsduringcurrentusefromageof
menopauseanduptoage69,per1000womenwith5yearsor10yearsuseofHRT
Risksassociatedwithcombinedestrogen–progestogenHRT
Durationof
Totalcasesper
HRTuse(years)
1000womenwith
noHRTuse*
(RR=1)
Cancerrisks
Breastcancer
KǀĞƌĂůůĐŽŵďŝŶĞĚ,Zd
5
13
Currentusefromage50
10
27
5
63
Totalriskfromage50to
69(HRTuse+pastuse)
10
63
^ĞƋƵĞŶƚŝĂů,Zd
5
13
Currentusefromage50
10
27
5
63
Totalriskfromage50to
69(HRTuse+pastuse)
10
63
ŽŶƚŝŶƵŽƵƐĐŽŵďŝŶĞĚ,Zd
5
13
Currentusefromage50
10
27
5
63
Totalrisktofromage50
to69(HRTuse+pastuse)
10
63
EndometrialCancer
5
2
age50–59
10
4
5
3
age60–69
10
6
OvarianCancer
5
2
age50–59
10
4
5
3
age60–69
10
6
Cardiovascularrisks
Venousthromboembolism(VTE)§
age50–59
5
5
age60–69
5
8
Stroke
age50–59
5
4
age60–69
5
9
Coronaryheartdisease(CHD)
age50–59
5
9
age60–69
5
18
age70–79
5
29
Benefits͐
Fractureoffemur
age50–59
5
1.5
age60Ͳ69
5
5.5
Totalcases
Extracases
Riskratio(RR)
(range)per1000
per1000women
(95%CI)‡
womenusing
usingHRT
Endocrine system
HRT†
21
+8
1.62
47
+20
1.74
80
+17
1.27
97
+34
1.54
20
+7
1.54
44
+17
1.63
77
+14
1.22
92
+29
1.46
23
+10
1.77
52
+25
1.93
83
+20
1.32
103
+40
1.63
1ͼ0(0ͼ8–1ͼ2)4
2(2–3)
NS
4(4–5)
NS
1ͼ1(0ͼ9–1ͼ2)
1ͼ0(0ͼ8–1ͼ2)4
3(2–4)
NS
7(5–7)
NS
1ͼ1(0ͼ9–1ͼ2)
2(2–3)
+<1
1.1(1.0–1.3)
5(4–6)
+1
1ͼ3(1ͼ1–1ͼ5)
3(3–4)
+<1
1.1(1.0–1.3)
8(7–9)
+2
1ͼ3(1ͼ1–1ͼ5)
12(10–15)
+7
2ͼ3(1ͼ8–3ͼ0)
18(15–24)
+10
5(5–6)
+1
1.3(1.1–1.4)
12(10–13)
+3
12(7–19)
NS
1ͼ3(0ͼ8–2ͼ1)
18(13–25)
NS
1ͼ0(0ͼ7–1ͼ4)
44(29–61)
+15
1ͼ5(1ͼ0–2ͼ1)
1(0.8–1.5)
NS
0ͼ7(0ͼ5–1.0)
4(3Ͳ5.5)
NS
RisksassociatedwithestrogenͲonlyHRTuse
Durationof
Totalcasesper
HRTuse
1000womenwith
(years)
noHRTuse*
(RR=1)
Cancerrisks
Endocrine system
Breastcancer
5
13
Currentusefromage50
10
27
Totalriskfromage50to
5
63
age69
10
63
(HRTuse+pastuse)
Endometrialcancer
5
2
age50–59
10
4
5
3
age60–69
10
6
Ovariancancer
5
2
age50–59
10
4
5
3
age60–69
10
6
Cardiovascularrisks
Venousthromboembolism(VTE)
age50–59
5
5
age60–69
5
8
Stroke
age50–59
5
4
age60–69
5
9
Coronaryheartdisease(CHD)
age50–59
5
14
age60–69
5
31
age70–79
5
44
Benefits͐
Fractureoffemur
age50–59
5
0.5
age60Ͳ69
5
5.5
*Backgroundincidencefrom:HospitalAdmissionsinEngland(HES)forstrokeandVTE;placeboarmsofWomen'sHealth
Initiative(WHI)trialforcoronaryheartdisease(CHD)andfracture;theInternationalAgencyResearchonCancer(IARC)for
ovariancancerandendometrialcancer;andfromOfficeforNationalStatistics(ONS)forEnglandfor2015,calculatedfor
neverͲusersintheCollaborativeGrouponHormonalFactorsinBreastCancermetaͲanalysisforbreastcancer.
†Bestestimateandrangebasedonrelativeriskand95%confidenceintervals(CI).
‡RiskraƟosand95%CIfrom:metaͲanalysisofprospectiveobservationalstudiesforbreastcancer(95%CInotavailable);
metaͲanalysesofRCTsandobservationalstudiesforendometrialcancer,ovariancancerandVTE;metaͲanalysesof
randomisedcontrolledtrials(RCTs)forstroke;andfromWHItrialforCHDandfracturerisk.
§LatestevidencesuggeststhattransdermalHRTproductshavealowerriskofVTEthanoralpreparations.
͐MenopausalsymptomreliefisnotincludedinthistablebutisakeybenefitofHRTandwillplayamajorpartinthe
decisiontoprescribeHRT.
NS=nonͲsignificantdifference.
ZĞƉƌŽĚƵĐĞĚǁŝƚŚƉĞƌŵŝƐƐŝŽŶŽĨƚŚĞD,ZƵŶĚĞƌƚŚĞƚĞƌŵƐŽĨƚŚĞKƉĞŶ'ŽǀĞƌŶŵĞŶƚ>ŝĐĞŶĐĞ;K'>Ϳǀϯ͘Ϭ
Totalcases
Extracases
Riskratio(RR)
(range)per1000
per1000women
(95%CI)‡
womenusing
usingHRT
HRT†
16
+3
1.2
34
+7
1.33
68
+5
1.08
74
+11
1.17
6(5–7)
+4
3.0(2.5–3.6)
36(25–52)
+32
9.0(6.3–12.9)
9(8–11)
+6
3.0(2.5–3.6)
54(38–77)
+48
9.0(6.3–12.9)
2
+<1
1.1(1.0–1.3)
5(5–6)
+1
1ͼ3(1ͼ2–1ͼ5)
3
+<1
1.1(1.0–1.3)
8(7–9)
+2
1ͼ3(1ͼ2–1ͼ5)
7(5–9)
+2
1.3(1.0–1.7)
10(8–14)
+2
5(5–6)
+1
1.3(1.0–1.4)
12(10–13)
+3
8(6–15)
NS
0ͼ6(0ͼ4–1ͼ1)
28(22–37)
NS
0ͼ9(0ͼ7–1ͼ2)
48(35–66)
NS
1ͼ1(0ͼ8–1ͼ5)
0.3(0.2–0.5)
0
0ͼ6(0ͼ4–0ͼ9)
3(2Ͳ5)
–2
Reasons to stop HRT
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
arm);
. 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 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
95 mmHg;
. prolonged immobility after surgery or leg injury;
. detection of a risk factor which contra-indicates
treatment.
Ethinylestradiol
Ethinylestradiol p. 802 (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
menstrual disorders.
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
Raloxifene hydrochloride p. 796 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
modulators
There are two main groups of progestogen, progesterone and
its analogues (dydrogesterone and medroxyprogesterone
acetate p. 856) and testosterone analogues (norethisterone
p. 806 and norgestrel). The newer progestogens (desogestrel
p. 850, norgestimate, and gestodene) are all derivatives of
norgestrel; levonorgestrel p. 851 is the active isomer of
norgestrel and has twice its potency. Progesterone p. 808
and its analogues are less androgenic than the testosterone
derivatives and neither progesterone nor dydrogesterone
causes virilisation.
Where endometriosis requires drug treatment, it may
respond to a progestogen, e.g. norethisterone, administered
on a continuous basis. Danazol p. 783 and gonadorelin
analogues are also available.
Although oral progestogens have been used widely for
menorrhagia (see Heavy menstrual bleeding p. 796) they are
relatively ineffective compared with tranexamic acid p. 117
or, particularly where dysmenorrhoea is also a factor,
mefenamic acid p. 1208; the levonorgestrel-releasing intra-
uterine system may be particularly useful for women also
requiring contraception. 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 also been advocated for the alleviation
of premenstrual symptoms, but no convincing physiological
basis for such treatment has been shown.
Progestogens have been used for the prevention of
miscarriage in women with a history of recurrent miscarriage
but there is no evidence of benefit and they are not
recommended for this purpose. In pregnant women with
antiphospholipid antibody syndrome who have suffered
recurrent miscarriage, administration of low-dose aspirin
p. 130 and a prophylactic dose of a low molecular weight
heparin may decrease the risk of fetal loss (use under
specialist supervision only).
Hormone replacement therapy
In women with a uterus a progestogen needs to be added to
Endocrine system
long-term oestrogen therapy for hormone replacement, to
prevent cystic hyperplasia of the endometrium and possible
transformation to cancer; it can be added on a cyclical or a
continuous basis. Combined packs incorporating suitable
progestogen tablets are available.
Oral contraception
Desogestrel p. 850, gestodene, levonorgestrel p. 851,
norethisterone p. 806, and norgestimate are used in
combined oral contraceptives and in progestogen-only
contraceptives.
Cancer
Progestogens also have a role in neoplastic disease.
Progesterone receptor modulators
Ulipristal acetate p. 849 is a progesterone receptor
modulator with a partial progesterone antagonist effect.
Ulipristal acetate is used in the pre-operative treatment of
moderate to severe symptoms of uterine fibroids (see
important safety information in ulipristal acetate). Ulipristal
acetate is also used as an hormonal emergency
contraceptive.
Endometriosis
Description of condition
Endometriosis is the growth of endometrial-like tissue
outside the uterus. Endometriosis is a condition affecting
women mainly of reproductive age and, although its exact
cause is unknown, it is an oestrogen-dependent condition
and is associated with menstruation. Endometriosis is
typically associated with symptoms such as pelvic pain,
painful periods and subfertility. Women with endometriosis
report pain, which can be frequent, chronic and severe, as
well as tiredness, more sick days, and a significant physical,
sexual, psychological and social impact. Endometriosis is an
important cause of subfertility and this can also have a
significant effect on quality of life.
Women may also have endometriosis without symptoms,
so it is difficult to know how common the disease is in the
population. It is also unclear whether endometriosis is
always progressive or can remain stable or improve with
time.
Aims of treatment
The aim of treatment is to reduce the severity of symptoms,
improve the quality of life, and to improve fertility if this is
affected.
Drug treatment
Management options for endometriosis include drug
treatment and surgery. Most drug treatments for
endometriosis work by suppressing ovarian function and are
contraceptive. Surgical treatment aims to remove or destroy
endometriotic lesions. The choice of treatment depends on
the woman’s preferences and priorities in terms of pain
management and fertility.
g A short trial (such as 3 months) of paracetamol or an
NSAID alone or in combination should be considered for
first-line management of endometriosis-related pain. If pain
relief is inadequate, consider other forms of pain
management and referral for further assessment.
Hormonal treatment (with a combined oral contraceptive
or a progestogen) should be offered to women with
suspected, confirmed or recurrent endometriosis. The
patient should be informed that hormonal treatment for
endometriosis can reduce pain and has no permanent
negative effect on subsequent fertility. If initial hormonal
treatment for endometriosis is not effective, not tolerated or
is contra-indicated, the woman should be referred to a
Endocrine system
gynaecologist or specialist endometriosis service for possible
further treatment, which could include other hormonal
treatments or surgery. h For use of drugs to treat
neuropathic pain, see Neuropathic pain.
Surgery
g Women with suspected or confirmed endometriosis
should be asked about their symptoms, preferences and
priorities with respect to pain and fertility, to guide surgical
decision-making. For deep endometriosis involving the
bowel, bladder or ureter, gonadotropin-releasing hormones
given for 3 months before surgery should be considered.
Excision rather than ablation should be considered to treat
endometriomas, taking into account the woman’s desire for
fertility and her ovarian reserve. After laparoscopic excision
or ablation of endometriosis, consider hormonal treatment
(with, for example, a combined hormonal contraceptive), to
prolong the benefits of surgery and manage symptoms.
A hysterectomy may be indicated if, for example, the
woman has adenomyosis or heavy menstrual bleeding that
has not responded to other treatments. h
Surgical management if fertility is a priority
g If fertility is a priority, the management of
endometriosis-related subfertility should have
multidisciplinary involvement with input from a fertility
specialist. Women with endometriosis who are trying to
conceive should not be offered hormonal treatment, because
it does not improve spontaneous pregnancy rates. h
Useful Resources
Endometriosis: diagnosis and management. National
Institute for Health and Care Excellence. NICE guidance 73.
February 2017.
www.nice.org.uk/guidance/ng73
Patient decision aid: Hormone treatment for
endometriosis symptoms—what are my options? National
Institute for Health and Care Excellence. September 2017.
www.nice.org.uk/about/what-we-do/our-programmes/nice-
guidance/nice-guidelines/shared-decision-making
Heavy menstrual bleeding
Description of condition
Heavy menstrual bleeding, also known as menorrhagia, is
excessive menstrual blood loss of 80 mL or more, or for a
duration of more than 7 days, which results in the need to
change menstrual products every 1–2 hours. Heavy
menstrual bleeding occurs regularly, every 24–35 days.
Drug treatment
g The choice of treatment should be guided by the
presence or absence of fibroids (including size, number and
location), polyps, endometrial pathology or adenomyosis,
other symptoms (such as pressure or pain), co-morbidities,
and patient preference.
In females with heavy menstrual bleeding and unidentified
pathology, fibroids less than 3 cm in diameter causing no
distortion of the uterine cavity, or suspected or diagnosed
adenomyosis, a levonorgestrel-releasing intra-uterine
system p. 851 is the first-line treatment option. Patients
should be advised that irregular menstrual bleeding can
occur particularly during the first months of use and that the
full benefit of treatment may take at least 6 months.
If a levonorgestrel-releasing intra-uterine system p. 851 is
unsuitable, either tranexamic acid p. 117, an NSAID, a
combined hormonal contraceptive, or a cyclical oral
progestogen should be considered. Progestogen-only
contraceptives may suppress menstruation and be beneficial
to females with heavy menstrual bleeding. A non-hormonal
treatment is recommended in patients actively trying to
conceive.
If drug treatment is unsuccessful or declined by the
patient, or if symptoms are severe, referral to a specialist for
alternative drug treatment or surgery should be considered.
In females with fibroids of 3 cm or more in diameter,
referral to a specialist should be considered. Treatment
options include tranexamic acid, an NSAID, ulipristal acetate
p. 849, a levonorgestrel-releasing intra-uterine system
p. 851, a combined hormonal contraceptive, a cyclical oral
progestogen, uterine artery embolisation, or surgery.
Treatment choice depends on the size, number and location
of the fibroids, and severity of symptoms. If drug treatment
is required while investigations and definitive treatment is
being organised, either tranexamic acid, or an NSAID, or
both, can be given.
Intermittent ulipristal acetate can be offered to females
who are not eligible for surgery and have a haemoglobin
concentration of 10.2 g/100 mL (102 g/litre) or less. If the
haemoglobin concentration is more than 10.2 g/100 mL
(102 g/litre), ulipristal acetate may be considered. The use of
ulipristal acetate is associated with a risk of rare but serious
liver injury; liver function should be monitored during
treatment, see Important safety information, and Monitoring
requirements in ulipristal acetate. h
The effectiveness of drug treatment (excluding ulipristal
acetate) for heavy menstrual bleeding may be limited in
females with fibroids that are substantially greater than 3 cm
in diameter. g Treatment with a gonadotrophin-releasing
hormone analogue or ulipristal acetate before hysterectomy
and myomectomy should be considered if uterine fibroids
are causing an enlarged or distorted uterus. h
Useful Resources
Heavy menstrual bleeding: assessment and management.
National Institute for Health and Care Excellence. NICE
guideline 88. November 2018.
www.nice.org.uk/guidance/ng88
8.1 Female sex hormone
responsive conditions
Other drugs used for Female sex hormone responsive
conditions Clonidine hydrochloride, p. 156. Ulipristal acetate,
p. 849
CALCIUM REGULATING DRUGS › BONE
RESORPTION INHIBITORS
PDF pages 811, 812, 813, 814, 815, 816, 817, 818
