50 patch to be applied and started within 5 days of
onset of menstruation (or at any time if cycles have
ceased or are infrequent), then apply 1 patch twice
weekly, Evorel ® Conti patch to be applied, subsequent
courses are repeated without interval.
Menopausal symptoms in women with a uterus whose last
menstrual period occurred over 12 months previously |
Osteoporosis prophylaxis in women with a uterus whose
last menstrual period occurred over 12 months
▶ Adult: 1 tablet daily continuously, to be started at end
of scheduled bleed if changing from cyclical HRT
Menopausal symptoms in women with a uterus whose last
menstrual period occurred over 12 months previously |
Osteoporosis prophylaxis in women with a uterus whose
last menstrual period occurred over 12 months
▶ Adult: 1 tablet daily continuously, to be started at end
of scheduled bleed if changing from cyclical HRT
Menopausal symptoms in women with a uterus |
Osteoporosis prophylaxis in women with a uterus
▶ Adult: 1 tablet daily for 16 days, red tablets to be taken,
then 1 tablet daily for 12 days, white tablets to be
taken, subsequent courses are repeated without
interval; start treatment with red tablet at any time or
if changing from cyclical HRT, start treatment the day
after finishing oestrogen plus progestogen phase
Menopausal symptoms in women with a uterus |
Osteoporosis prophylaxis in women with a uterus
▶ Adult: 1 tablet daily for 12 days, blue tablets to be
taken, followed by 1 tablet daily for 10 days, white
tablet to be taken, then 1 tablet daily for 6 days, red
tablet to be taken, subsequent courses are repeated
l INTERACTIONS → Appendix 1: hormone replacement
EVOREL ® SEQUI Patients and carers should be advised on
the application of Evorel ® Sequi patches.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Clinorette (ReSource Medical UK Ltd)
Clinorette tablets | 84 tablet P £9.23
▶ Elleste Duet (Meda Pharmaceuticals Ltd)
Elleste Duet 1mg tablets | 84 tablet P £9.20
Elleste Duet 2mg tablets | 84 tablet P £9.20
Norethisterone acetate 1 mg, Estradiol 2 mg Elleste Duet Conti
tablets | 84 tablet P £17.02 DT = £17.02
Norethisterone acetate 1 mg, Estradiol 2 mg Kliofem tablets | 84 tablet P £11.43 DT = £17.02
▶ Kliovance (Novo Nordisk Ltd)
Norethisterone acetate 500 microgram, Estradiol 1 mg Kliovance
tablets | 84 tablet P £13.20 DT = £13.20
Novofem tablets | 84 tablet P £11.43
▶ Trisequens (Novo Nordisk Ltd)
Trisequens tablets | 84 tablet P £11.10
▶ Evorel Conti (Janssen-Cilag Ltd)
Estradiol 50 microgram per 24 hour, Norethisterone acetate
170 microgram per 24 hour Evorel Conti patches | 8 patch P £13.00 | 24 patch P £37.22 DT = £37.22
▶ Evorel Sequi (Janssen-Cilag Ltd)
Evorel Sequi patches | 8 patch P £11.09
The properties listed below are those particular to the
combination only. For the properties of the components
please consider, estradiol p. 756.
Menopausal symptoms in women with a uterus |
Osteoporosis prophylaxis in women with a uterus
▶ Adult: 1 tablet daily for 11 days, white tablet to be
taken; start on day 5 of menstruation (or at any time if
cycles have ceased or are infrequent), then 1 tablet
daily for 10 days, brown tablet to be taken, followed by
l INTERACTIONS → Appendix 1: hormone replacement
▶ Frequency not known Angioedema . dementia . gallbladder
disorder. myocardial infarction . neoplasms . stroke . venous thromboembolism
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Cyclo-Progynova (Meda Pharmaceuticals Ltd)
Cyclo-Progynova 2mg tablets | 21 tablet P £3.11
BNF 78 Female sex hormone responsive conditions 763
▶ Adult: 10–15 mg daily for 4–6 months or longer, to be
started on day 5 of cycle; increased to 20–25 mg daily if
required, dose only increased if spotting occurs and
reduced once bleeding has stopped
Dysfunctional uterine bleeding (to arrest bleeding)|
Menorrhagia (to arrest bleeding)
▶ Adult: 5 mg 3 times a day for 10 days
Dysfunctional uterine bleeding (to prevent bleeding)|
Menorrhagia (to prevent bleeding)
▶ Adult: 5 mg twice daily, to be taken from day 19 to day
▶ Adult: 5 mg 3 times a day for 3–4 cycles, to be taken
Premenstrual syndrome (but not recommended)
▶ Adult: 5 mg 2–3 times a day for several cycles, to be
▶ Females of childbearing potential: 5 mg 3 times a day, to
be started 3 days before expected onset (menstruation
occurs 2–3 days after stopping)
▶ Adult: 40 mg daily, increased if necessary to 60 mg
▶ BY DEEP INTRAMUSCULAR INJECTION
▶ Females of childbearing potential: 200 mg, to be
administered within first 5 days of cycle or immediately
after parturition (duration 8 weeks). To be injected into
the gluteal muscle, then 200 mg after 8 weeks if
▶ Females of childbearing potential: 350 micrograms daily,
dose to be taken at same time each day, starting on day
1 of cycle then continuously, if administration delayed
for 3 hours or more it should be regarded as a ‘missed
Avoid in patients with a history of liver tumours . breast
cancer (unless progestogens are being used in the
management of this condition). genital cancer (unless
progestogens are being used in the management of this
condition). history during pregnancy of idiopathic
jaundice . history during pregnancy of pemphigoid
gestationis (non-contraceptive indications). history
during pregnancy of severe pruritus (non-contraceptive
indications). when used as a contraceptive, history of
breast cancer (can be used after 5 years if no evidence of
disease and non-hormonal contraceptive methods
▶ With oral use Acute porphyrias p. 1058 . severe arterial
disease . undiagnosed vaginal bleeding
(progestogens can decrease glucose tolerance—monitor
patient closely). epilepsy . history of depression . hypertension . migraine . susceptibility to
thromboembolism (particular caution with high dose)
▶ When used for contraception active trophoblastic disease
jaundice in pregnancy . malabsorption syndromes . past
▶ With intramuscular use for contraception disturbances of lipid
metabolism . history during pregnancy of deterioration of
otosclerosis . history during pregnancy of pruritus . possible risk of breast cancer
▶ Use as a contraceptive in co-morbidities The product literature
advises caution in patients with history of
thromboembolism, hypertension, diabetes mellitus and
migraine; evidence for caution in these conditions is
▶ Breast cancer risk with contraceptive use There is a small
increase in the risk of having breast cancer diagnosed in
earlier diagnosis. The most important risk factor appears
to be the age at which the contraceptive is stopped rather
than the duration of use; the risk disappears gradually
during the 10 years after stopping and there is no excess
risk by 10 years. A possible small increase in the risk of
breast cancer should be weighed against the benefits.
l INTERACTIONS → Appendix 1: norethisterone
▶ Common or very common Menstrual cycle irregularities
▶ Frequency not known Hepatic cancer.thromboembolism
▶ With intramuscular use Abdominal distension . depressed
disorder. nervousness .rash . weight change
▶ With oral use Masculinisation of female fetuses and other
defects reported with non-contraceptive use.
l BREAST FEEDING Progestogen-only contraceptives do not
affect lactation. Higher doses (used in malignant
conditions) may suppress lactation and alter milk
composition—use lowest effective dose.
▶ With intramuscular use Withhold breast-feeding for
neonates with severe or persistent jaundice requiring
l HEPATIC IMPAIRMENT When used as a contraceptive;
caution in severe liver disease and recurrent cholestatic
jaundice, avoid in liver tumour. Avoid in noncontraceptive indications.
l RENAL IMPAIRMENT Use with caution in noncontraceptive indications.
764 Sex hormone responsive conditions BNF 78
Diarrhoea and vomiting with oral contraceptives Vomiting and
persistent, severe diarrhoea can interfere with the
absorption of oral progestogen-only contraceptives. If
vomiting occurs within 2 hours of taking an oral
progestogen-only contraceptive, another pill should be
taken as soon as possible. If a replacement pill is not taken
within 3 hours of the normal time for taking the
progestogen-only pill, or in cases of persistent vomiting or
very severe diarrhoea, additional precautions should be
used during illness and for 2 days after recovery.
Starting routine for oral contraceptives One tablet daily, on a
continuous basis, starting on day 1 of cycle and taken at
the same time each day (if delayed by longer than 3 hours
contraceptive protection may be lost). Additional
contraceptive precautions are not required if
norethisterone is started up to and including day 5 of the
menstrual cycle; if started after this time, additional
contraceptive precautions are required for 2 days.
Changing from a combined oral contraceptive Start on the day
following completion of the combined oral contraceptive
course without a break (or in the case of ED tablets
After childbirth Oral progestogen-only contraceptives can
be started up to and including day 21 postpartum without
the need for additional contraceptive precautions. If
started more than 21 days postpartum, additional
contraceptive precautions are required for 2 days.
Contraceptives by injection Full counselling backed by patient
information leaflet required before administration—
likelihood of menstrual disturbance and the potential for a
delay in return to full fertility. Delayed return of fertility
and irregular cycles may occur after discontinuation of
treatment but there is no evidence of permanent
Missed oral contraceptive pill The following advice is
recommended: ‘If you forget a pill, take it as soon as you
remember and carry on with the next pill at the right time.
If the pill was more than 3 hours overdue you are not
protected. Continue normal pill-taking but you must also
use another method, such as the condom, for the next
The Faculty of Sexual and Reproductive Healthcare
recommends emergency contraception if one or more
progestogen-only contraceptive tablets are missed or
taken more than 3 hours late and unprotected intercourse
has occurred before 2 further tablets have been correctly
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension
Norethisterone enantate 200 mg per 1 ml Noristerat 200mg/1ml
solution for injection ampoules | 1 ampoule P £4.05
▶ Norethisterone (Non-proprietary)
Norethisterone 5 mg Norethisterone 5mg tablets | 30 tablet P £2.40 DT = £2.35
Norethisterone 350 microgram Noriday 350microgram tablets |
Norethisterone 5 mg Primolut N 5mg tablets | 30 tablet P £2.26 DT = £2.35
Norethisterone 5 mg Utovlan 5mg tablets | 30 tablet P £1.40
DT = £2.35 | 90 tablet P £4.21
Combinations available: Estradiol with norethisterone, p. 762
Infertility due to inadequate luteal phase
▶ Adult: 1 applicatorful daily, to be started either after
documented ovulation or on day 18–21 of cycle, in
vitro fertilisation, daily application continued for
30 days after laboratory evidence of pregnancy
Premenstrual syndrome | Post-natal depression
▶ Adult: 200–800 mg daily, doses above 200 mg to be
given in 2 divided doses, for premenstrual syndrome
start on day 12–14 and continue until onset of
menstruation (but not recommended); rectally if
barrier methods of contraception are used, in patients
who have recently given birth or in those who suffer
from vaginal infection or recurrent cystitis
GESTONE ® SOLUTION FOR INJECTION
Dysfunctional uterine bleeding
▶ BY DEEP INTRAMUSCULAR INJECTION
▶ Adult: 5–10 mg daily for 5–10 days until 2 days before
expected onset of menstruation, to be administered
Recurrent miscarriage due to inadequate luteal phase
(but not recommended) or following in vitro fertilisation
or gamete intra-fallopian transfer
▶ BY DEEP INTRAMUSCULAR INJECTION
▶ Adult: 25–100 mg 2–7 times a week from day 15, or day
of embryo or gamete transfer, until 8–16 weeks of
pregnancy, to be administered into buttocks;
Supplementation of luteal phase during assisted
reproductive technology (ART) treatment in women for
whom vaginal preparations are inappropriate
▶ BY SUBCUTANEOUS INJECTION, OR BY INTRAMUSCULAR
▶ Adult: 25 mg once daily from day of oocyte retrieval up
Luteal support as part of an Assisted Reproductive
Technology (ART) treatment programme
▶ Adult: 100 mg 3 times a day, to be started the day after
oocyte retrieval, and continued for 30 days once
Progestogenic opposition of oestrogen HRT
▶ Adult: 200 mg once daily on days 15–26 of each 28-day
oestrogen HRT cycle, alternatively 100 mg once daily
on days 1–25 of each 28-day oestrogen HRT cycle
Supplementation of luteal phase during assisted
reproductive technology (ART) cycles
▶ Adult: 1 capsule 3 times a day from day of embryo
transfer until at least week 7 of pregnancy up to week
l CONTRA-INDICATIONS Acute porphyrias p. 1058 . avoid in
patients with a history of liver tumours . breast cancer
(unless progestogens are being used in the management of
this condition). genital cancer (unless progestogens are
being used in the management of this condition). history
BNF 78 Female sex hormone responsive conditions 765
during pregnancy of idiopathic jaundice . history during
pregnancy of pemphigoid gestationis . history during
arterial disease .thrombophlebitis . undiagnosed vaginal
l CAUTIONS Asthma . cardiac dysfunction . conditions that
may worsen with fluid retention . diabetes (progestogens
▶ With oral use Headache . menstrual cycle irregularities
▶ With vaginal use Breast pain . drowsiness . gastrointestinal
▶ With oral use Depression . nausea
▶ With intramuscular use Alopecia . breast changes . cervical
irregularities . nausea . oedema . protein catabolism . skin
▶ With rectal use Diarrhoea . flatulence
▶ With vaginal use Leakage of the pessary base . menstrual
cycle irregularities . vulvovaginal pain
l PREGNANCY Not known to be harmful.
l BREAST FEEDING Avoid—present in milk.
l HEPATIC IMPAIRMENT Avoid in hepatic impairment. Avoid
in active liver disease including disorders of hepatic
excretion (e.g. Dublin-Johnson or Rotor Syndromes),
infective hepatitis (until liver function returns to normal)
l RENAL IMPAIRMENT Use with caution.
l DIRECTIONS FOR ADMINISTRATION
▶ With oral use Capsules should be taken at bedtime on an
▶ With oral use Patient counselling is advised for
progesterone capsules (administration).
l NATIONAL FUNDING/ACCESS DECISIONS
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (October
2016) that progesterone (Lutigest ®) is accepted for use
within NHS Scotland for luteal support as part of an
assisted reproductive technology (ART) treatment
program for infertile women. This advice is contingent
upon the continuing availability of the Patient Access
Scheme (PAS) in NHS Scotland or a list price that is
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (July 2018)
that progesterone (Lubion ®) is accepted for use within
NHS Scotland for luteal support as part of an Assisted
Reproductive Technology (ART) treatment program in
infertile women who are unable to use or tolerate vaginal
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (May 2017)
that micronised progesterone (Utrogestan Vaginal ®) is
accepted for use within NHS Scotland for supplementation
of the luteal phase during Assisted Reproductive
Technology cycles in women. This advice is contingent
upon the continuing availability of the Patient Access
Scheme in Scotland or a list price that is equivalent or
l LESS SUITABLE FOR PRESCRIBING
▶ With vaginal use Progesterone pessaries are less suitable for
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Cyclogest (L.D. Collins & Co. Ltd)
Progesterone 200 mg Cyclogest 200mg pessaries | 15 pessary P £8.95 DT = £8.95
Progesterone 400 mg Cyclogest 400mg pessaries | 15 pessary P £12.96 DT = £12.96
▶ Lutigest (Ferring Pharmaceuticals Ltd)
Progesterone 100 mg Lutigest 100mg vaginal tablets |
21 pessary P £19.50 DT = £19.50
Progesterone 50 mg per 1 ml Gestone 50mg/1ml solution for
injection ampoules | 10 ampoule P £45.00
Gestone 100mg/2ml solution for injection ampoules | 10 ampoule P £45.00
Progesterone 80 mg per 1 gram Crinone 8% progesterone vaginal
gel | 15 unit dose P £30.83 DT = £30.83
EXCIPIENTS: May contain Arachis (peanut) oil
▶ Utrogestan (Besins Healthcare (UK) Ltd)
Progesterone 100 mg Utrogestan 100mg capsules | 30 capsule P £5.13 DT = £5.13
Progesterone 200 mg Utrogestan 200mg vaginal capsules with
applicators | 21 capsule P £21.00 DT = £21.00
l DRUG ACTION Anti-oestrogen which induces
gonadotrophin release by occupying oestrogen receptors
in the hypothalamus, thereby interfering with feedback
mechanisms; chorionic gonadotrophin is sometimes used
Female infertility due to ovulatory dysfunction
▶ Adult (female): 50 mg once daily for 5 days, to be started
at any time if no recent uterine bleeding or on or
around the fifth day of cycle if progestogen-induced
bleeding is planned or if spontaneous uterine bleeding
occurs, then 100 mg once daily if required for 5 days,
this second course to be given at least 30 days after the
first course, only in the absence of ovulation; most
patients who are going to respond will do so to first
course, 3 courses should constitute adequate
766 Sex hormone responsive conditions BNF 78
therapeutic trial; long-term cyclical therapy not
recommended (beyond a total of 6 cycles).
The CSM has recommended that clomifene should not
normally be used for longer than 6 cycles (possibly
increased risk of ovarian cancer).
l CONTRA-INDICATIONS Abnormal uterine bleeding of
undetermined cause . hormone-dependent tumours . ovarian cysts
l CAUTIONS Ectopic pregnancy . incidence of multiple births
increased (consider ultrasound monitoring). ovarian
hyperstimulation syndrome . polycystic ovary syndrome
(cysts may enlarge during treatment, also risk of
exaggerated response to usual doses). uterine fibroids
irregularities . mood altered . nausea . neoplasms . nervous
system disorders . optic neuritis . ovarian and fallopian
disorders . visual impairment (discontinue and initiate
ophthalmological examination). vomiting
l CONCEPTION AND CONTRACEPTION Exclude pregnancy
l PREGNANCY Possible effects on fetal development.
l BREAST FEEDING May inhibit lactation.
l HEPATIC IMPAIRMENT Manufacturer advises avoid in liver
disease or history of liver dysfunction.
Conception and contraception Patients planning to
conceive should be warned that there is a risk of multiple
pregnancy (rarely more than twins).
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Clomifene citrate (Non-proprietary)
Clomifene citrate 50 mg Clomifene 50mg tablets | 30 tablet P £10.15 DT = £10.15
Clomifene citrate 50 mg Clomid 50mg tablets | 30 tablet P £10.15 DT = £10.15
Androgens cause masculinisation; they may be used as
replacement therapy in castrated adults and in those who are
hypogonadal due to either pituitary or testicular disease. In
the normal male they inhibit pituitary gonadotrophin
secretion and depress spermatogenesis. Androgens also have
an anabolic action which led to the development of anabolic
Androgens are useless as a treatment of impotence and
impaired spermatogenesis unless there is associated
hypogonadism; they should not be given until the
hypogonadism has been properly investigated. Treatment
should be under expert supervision.
When given to patients with hypopituitarism they can lead
to normal sexual development and potency but not to
fertility. If fertility is desired, the usual treatment is with
gonadotrophins or pulsatile gonadotrophin-releasing
hormone which will stimulate spermatogenesis as well as
Intramuscular depot preparations of testosterone esters
are preferred for replacement therapy. Testosterone
enantate, propionate or undecanoate, or alternatively
Sustanon ®, which consists of a mixture of testosterone esters
and has a longer duration of action, may be used.
Cyproterone acetate p. 770 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 male contraceptive);
abnormal sperm forms are produced. Fully informed consent
is recommended and an initial spermatogram. As hepatic
tumours have been produced in animal studies, careful
consideration should be given to the risk/benefit ratio before
treatment. Cyproterone acetate is also licensed for use alone
in patients with metastatic prostate cancer refractory to
gonadorelin analogue therapy and has been used as an
adjunct in prostatic cancer and in the treatment of acne and
Dutasteride p. 787 and finasteride p. 787 are alternatives to
alpha-blockers particularly in men with a significantly
enlarged prostate. Finasteride is also licensed for use with
doxazosin p. 783 in the management of benign prostatic
A low strength of finasteride is licensed for treating malepattern baldness in men.
Anabolic steroids have some androgenic activity but they
cause less virilisation than androgens in women. They are
used in the treatment of some aplastic anaemias. Anabolic
steroids have been given for osteoporosis in women but they
are no longer advocated for this purpose.
The protein-building properties of anabolic steroids have
not proved beneficial in the clinical setting. Their use as
body builders or tonics is unjustified; some athletes abuse
l CONTRA-INDICATIONS Breast cancer in males . history of
liver tumours . hypercalcaemia . prostate cancer
hastened and may result in short stature)—statural growth
and sexual development should be monitored . skeletal
metastases—risk of hypercalcaemia or hypercalciuria (if
this occurs, treat appropriately and restart treatment once
normal serum calcium concentration restored). sleep
apnoea . stop treatment or reduce dose if severe
polycythaemia occurs .tumours—risk of hypercalcaemia or
hypercalciuria (if this occurs, treat appropriately and
restart treatment once normal serum calcium
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