Summary for UKPID
PROGESTOGENS
Helen Seymour, BPharm (Hons)
National Poisons Information Service (Newcastle Centre)
Regional Drug & Therapeutics Centre
Wolfson Building
Claremont Place
Newcastle upon Tyne
NE1 4LP
UK
This monograph has been produced by staff of a National Poisons
Information Service Centre in the United Kingdom. The work was
commissioned and funded by the UK Departments of Health, and was
designed as a source of detailed information for use by poisons
information centres.
Peer review group: Directors of the UK National Poisons Information
Service.
SUMMARY
Type of product
Used for a number of purposes, including treatment of amenorrhea,
abnormal uterine bleeding, contraception, malignant disease and
menopausal symptoms.
Ingredients
A progestogen.
Toxicity
Very low.
Features
May cause nausea and vomiting.
Rarely, withdrawal bleeding may occur in pre-pubertal girls.
Treatment
None required.
SUBSTANCE
Progestogen
ORIGIN OF SUBSTANCE
Synthetic
NAME
Brand Name/Generic Name
Cyclogest/ Progesterone
Depo-Provera/Medroxyprogesterone
Depostat/ Gestronol hexanoate
Duphaston/ Dydrogesterone
Duphaston HRT/Dydrogesterone
Farlutal/ Medroxyprogesterone
Femulen/ Ethynodiol diacetate
Gestone/ Progesterone
Megace/ Megesterol Acetate
Menzol/ Norethisterone
Micronor HRT/ Norethisterone
Micronor/ Norethisterone
Microval/ Levonorgestrel
Mirena/Levonorgestrel
Neogest/ Norgestrel
Norgeston/ Levonorgestrel
Noriday/ Norethisterone
Noristat/ Norethisterone
Norplant/ Levonorgestrel
Primolut N/ Norethisterone
Proluten Depot/ Hydroxyprogesterone Hexanoate
Provera/ Medroxyprogesterone Acetate
Utovlan/ Norethisterone
CHEMICAL GROUP
Progestogens
BNF 6.4.1.2
Progestogen-Only contraceptives
BNF 7.3.2
Progestogens
BNF 8.3.2
SUBSTANCE IDENTITY
REFERENCE NUMBER
CAS
Product licence number
Cyclogest Pessaries 200mg 2343/0001
Cyclogest Pessaries 400mg 2343/0002
Depo-Provera 150mg/ml 0032/0082
Depostat 200mg in 2ml 0053/0190
Duphaston/Duphaston HRT 0512/5004R
Farlutal 100mg tablets 3433/0056
Farlutal 250mg tablets 3433/0058
Farlutal 500mg tablets 3433/0080
Farlutal 200mg/ml, 2.5ml 3433/0045
Farlutal 200mg/ml, 5ml 3433/0045
Femulen 500mcg 08821/0015
Gestone 25mg 3194/0061
Gestone 50mg 3194/0062
Gestone 100mg 3194/0063
Megace 40mg tablets 0125/0144
Megace 160mg tablets 0125/0173
Menzol 5mg tablets
Micronor Oral Contraceptives 0242/0234
Micronor HRT 0242/0241
Microval 0011/0040
Mirena 0484/0025
Neogest 0053/0062
Norgeston 0053/0068
Noriday 088210036
Noristerat 0053/0095
Norplant 0109/0249
Primolut N 0053/5033R
Provera 2.5mg 0032/0168
Provera 5mg 0032/5035R
Provera 10mg 0032/0151
Provera 100mg 0032/0111
Provera 200mg 0032/0112
Provera 400mg 0032/0131
Proluten Depot 250mg 0053/5031R
Proluten Depot 500mg 0053/5032R
MANUFACTURER
Bristol-Myers Squibb
Pharmaceuticals Ltd
141-149 Staines Rd
Hounslow
Middlesex
TW3 3JA
0181 5727422
Ferring Pharmaceuticals Ltd
Greville House
Hatton Road
Feltham
Middlesex
TW14 9PX
0181 8931543
Hoechst Rousell Ltd
Broadwater Park
Denham
Uxbridge
Middlesex
UB9 5HP
01895 834343
Janssen-Cilag Ltd
PO Box 79,
Saunderton,
High Wycombe,
Bucks
HP14 4HJ
01494 567567
Organon Laboratories Ltd
Cambridge Science Park,
Milton Road,
Cambridge
CB4 4FL
01223 423445
Ortho
see Janssen-Cilag
P-D
Parke-Davis Medical,
Lambert Court,
Chestnut Avenue,
Eastleigh,
Hants
SO53 3ZQ
01703 620500
Pharmacia-Leiras Ltd
Pharmacia & Upjohn
Davy Avenue
Knowlhill
Milton Keynes
MK5 8PH
01908 661101
Roussell
see Hoechst-Roussell
Schering Health Care Ltd
The Brow,
Burgess Hill,
West Sussex
RH15 9NE
01444 232323
Schwarz Pharma Ltd
Schwarz House
East Street
Chesham
Bucks
HP5 1DG
01494 772071
Searle Pharmaceuticals
PO Box 53,
Lane End Road,
High Wycombe,
Bucks
HP12 4HL
01494 521124
Solvay Healthcare Ltd
Hamilton House
Gaters Hill
West End
Southampton
SO18 3JD
01703 472281
Upjohn Ltd
See Pharmacia-Upjohn
Wyeth Laboratories
Huntercombe Lane South,
Taplow,
Maidenhead,
Berks
SL6 0PH
01628 604377
PRESENTATION
Form
Cyclogest Pessaries 200mg pessaries
Cyclogest Pessaries 400mg pessaries
Depo-Provera 150mg/1ml, 3.3ml injection
Depostat100mg/ml, 2ml injection
Duphaston/Duphaston HRT 10mg tablets
Farlutal 100mg,250mg, 500mg tablets
Farlutal 200mg/ml, 2.5ml & 5ml injection
Femulen 5mg tablets
Gestone 25mg injection
Gestone 50mg injection
Gestone 100mg injection
Megace 40mg, 160mg tablets
Menzol 5mg tablets
Micronor Oral Contraceptives tablets
Micronor HRT tablets
Microval 30mcg tablets
Mirena 20mcg/24hours intra-uterine system
Neogest 75mcg tablets
Norgeston 30 mcg tablets
Noriday 350mcg tablets
Noristerat 200mg/ml injection
Norplant 38mg implant capsule
Primolut N 5mg tablets
Provera 2.5mg tablets
Provera 5mg tablets
Provera 10mg tablets
Provera 100mg tablets
Provera 200mg tablets
Provera 400mg tablets
Proluten Depot 250mg injection
Proluten Depot 500mg injection
Utovlan 5mg tablets
Pack sizes
Cyclogest Pessaries 200mg - 15
Cyclogest Pessaries 400mg - 15
Depostat - 1
Depo-Provera 150mg, 3.3ml - 1
Depostat - 1
Duphaston - 60
Duphaston HRT - 42
Farlutal 100mg tablets - 20; 50
Farlutal 500mg tablets - 56
Farlutal 200mg/ml, 2.5ml - 1
Farlutal 200mg/ml, 5ml - 1
Femulen - 28
Gestone 25mg - 1
Gestone 50mg - 1
Gestone 100mg - 1
Megace 40mg - 20
Megace 160mg - 30
Menzol - 3 x 24; 3 x60
Micronor Oral Contraceptives - 3 x 28
Micronor HRT - 3 x 12
Microval - 35
Mirena - 1
Neogest - 35
Norgeston - 35
Noriday - 3 x 28
Noristerat - 1
Norplant - 6 implants
Primolut N - 30
Provera 2.5mg - 30
Provera 5mg - 10
Provera 10mg - 10; 90
Provera 100mg - 60
Provera 200mg - 30
Provera 400mg - 30
Proluten Depot 250mg - 1
Proluten Depot 500mg - 1
PHYSIOCHEMICAL PROPERTIES
Chemical structure
Dydrogesterone - 6-Dehydro-9ß,10alpha-progesterone
Ethynodiol acetate - 19-Nor-17alpha-pregn-4-en-20-yne-3ß
Gestronol - NIF
Hydroxyprogesterone hexanoate - 17alpha-Hydroxypregn-4-ene-3,20-
dione hexanoate
Levonorgestrel - 13-Ethyl-17ß-hydroxy-18,19-dinor-17alpha-pregn-
4-en-20-yn-3-one
Medroxyprogesterone acetate - 17alpha-Hydroxy-6alpha-methylpregn-
4-ene-3,20-dione acetate
Megestrol Acetate - 6-Methyl-3,20-dioxopregna-4,6-dien-17alpha-yl
acetate
Norgestrel - (±)-13-Ethyl-17ß-hydroxy-18,19-dinor-17alpha-pregn-
4-en-20-yn-3-one
Norethisterone - 17alpha-Ethinyl-19-nortestosterone, 17ß-hydroxy-
19-nor-17alpha-pregn-4-en-20-yn-3-one, 17alpha-ethinyl-17ß-
hydroxy-19-nor-androst-4-en-3-one
Progesterone - Pregn-4-ene-3,20-dione
Physical structure at room temperature
All are solid
Colour
Dydrogesterone - white to pale yellow
Ethynodiol acetate - white or almost white
Gestronol - NIF
Hydroxyprogesterone hexanoate - white or creamy white
Levonorgestrel - white or almost white
Megestrol Acetate - white or creamy-white
Medroxyprogesterone acetate - white or off-white
Norgestrel - white or almost white
Norethisterone - white or yellowish-white
Progesterone - white or slightly yellowish-white
Odour
Dydrogesterone - odourless or almost odourless
Ethynodiol acetate - odourless or almost odourless
Gestronol - NIF
Hydroxyprogesterone hexanoate - odourless or almost odourless
Levonorgestrel - odourless
Megestrol Acetate - odourless or almost odourless
Medroxyprogesterone acetate - odourless
Norgestrel - almost odourless
Norethisterone - odourless
Progesterone - odourless
Viscosity
NA
pH
NA
Solubility
Dydrogesterone - Practically insoluble in water; soluble 1 in 40 of
alcohol, 1 in 2 of chloroform, and 1 in 200 of ether; soluble in
acetone; sparingly soluble in methyl alcohol; slightly soluble in
fixed oils
Ethynodiol acetate - very slightly soluble to practically insoluble in
water; soluble in alcohol; freely to very soluble in chloroform;
freely soluble in ether; sparingly soluble in fixed oils
Gestronol - NIF
Hydroxyprogesterone hexanoate - practically insoluble in water; freely
soluble in alcohol and ether; very soluble in chloroform; dissolves in
fixed oils and esters
Levonorgestrel - practically insoluble in water; slightly soluble in
alcohol, in acetone and in ether; soluble in chloroform; sparingly
soluble in methylene chloride.
Megestrol Acetate - practically insoluble in water; sparingly soluble
in alcohol; very soluble in chloroform; soluble in acetone; slightly
soluble in ether and in fixed oils.
Medroxyprogesterone acetate - practically insoluble in water;
sparingly soluble in alcohol and in methylalcohol; slightly soluble in
ether; freely soluble in chloroform; soluble in acetone and dioxan
Norgestrel - practically insoluble in water; the BP states that it is
slightly, and the USP that it is sparingly soluble in alcohol;
sparingly soluble in methylene chloride; freely soluble in chloroform
Norethisterone - practically insoluble in water; slight to sparingly
soluble in alcohol; soluble in chloroform and in dioxan; slightly
soluble in ether.
Progesterone - BP solublities are: practically insoluble in water;
freely soluble in dehydrated alcohol; very soluble in chloroform;
sparingly soluble in acetone, in ether and in fixed oils. USP
solubilities are: practically insoluble in water; soluble in alcohol,
in acetone and in dioxan; sparingly soluble in vegetable oils
USES
Indications
To prevent conception; as part of hormone replacement regimes; as a
hormone antagonist in malignant disease.
Therapeutic Dose
Contraceptive: 1 tablet (of whichever preparation prescribed) daily at
the same time each day, starting on 1st day of cycle then
continuously.
Dydrogesterone - Endometriosis, 10mg 2-3 times daily from 5th to 25th
day of cycle or continuously; Infertility, irregular cycles, 10mg
twice daily from 11th to 25th day for at least 6 cycles (but not
recommended); Habitual abortion, 10mg twice daily from day 11 to day
25 of cycle until conception, then continuously until 20th week of
pregnancy and gradually reduced; Dysfunctional uterine bleeding, 10mg
twice daily (together with an oestrogen) for 5-7 days to arrest
bleeding; 10mg twice daily (together with an oestrogen) from 11th to
25th day of cycle to prevent bleeding; Dysmenorrhoea, 10mg twice daily
from 5th to 25th day of cycle; Amenorrhoea, 10mg twice daily form 11th
to 25th day of cycle with oestrogen therapy from 1st to 25th day of
cycle; Pre-menstrual syndrome, 10mg twice daily from 12th to 26th day
of cycle, increased if necessary (but not recommended); HRT, 10mg
daily on days 15-28 of each 28-day oestrogen HRT cycle, increased to
10mg twice daily if withdrawal bleed is early or endometrial biopsy
shows inadequate progestational response.
Hydroxyprogesterone hexanoate - Habitual abortion, 250-500mg weekly by
slow intra-muscular injection during first half of pregnancy.
Medroxyprogesterone acetate - Dysfunctional uterine bleeding, 2.5-10mg
daily for 5-10 days beginning on 16th-21st day of cycle, repeated for
2 cycles, for secondary amenorrhoea repeat for 3 cycles; Mild to
moderate endometriosis, 10mg 3 times daily for 90 consecutive days,
beginning on 1st day of cycle; Endometrial, prostate and renal cancer,
100-500mg daily; Breast cancer, various doses in range 0.4-1.5g daily;
by deep intramuscular injection for malignant disease, various doses
in range 1g daily down to 250mg weekly.
Megestrol Acetate - Breast cancer, 160mg daily in single or divided
doses; endometrial cancer, 40-320mg daily in divided doses.
Norethisterone - Endometriosis, 10mg daily starting on 5th day of
cycle (increased if spotting occurs to 20-25mg daily, reduced once
bleeding has stopped); Menorrhagia, 5mg 3 times daily for 10 days to
arrest bleeding; to prevent bleeding 5mg twice daily from 19th to 26th
day; Dysmenorrhoea, 5mg 3 times daily from 5th to 24th day for 3-4
cycles; Pre-menstrual syndrome, 5mg 2-3 times daily from 19th to 26th
day for several cycles (but not recommended); Postponement of
menstruation, 5mg three times daily starting 3 days before anticipated
onset (menstruation occurs 2-3 days after stopping); HRT 1mg daily on
days 15-26 of each 28-day oestrogen HRT cycle; Breast cancer, 40mg
daily, increased to 60mg daily if required.
Progesterone - Pre-menstrual syndrome, pessaries - 200mg daily to
400mg twice daily starting on day 12-14 and continued until onset of
menstruation (but not recommended); rectally if barrier methods of
contraception are used, or if vaginal infection; Embryo transfer, deep
intramuscular injection as per data sheet.
Contraindications
Pregnancy (except where licensed);a history during pregnancy of
idiopathic jaundice or severe pruritis. Acute or severe chronic liver
diseases including liver tumours. Dubin-Johnson or Rotor syndrome.
Undiagnosed abnormal vaginal bleeding. Thrombo-embolic disorders,
thrombophlebitis, cerebrovascular disorders, coronary artery disease,
myocardial infarction, angina, hyperlipidaemia or a history of these
conditions.
Abuses
NIF
HAZARD/RISK CLASSIFICATION
NIF
PHARMACOKINETICS
Absorption
Dydrogesterone
NIF
Ethynodiol acetate
almost 100%
Gestronol
NIF
Hydroxyprogesterone hexanoate
90%
Megestrol Acetate
about 100%
Medroxyprogesterone acetate
<100%
Norgestrel
NIF
Norethisterone
100%
Progesterone - extensive
Distribution
Dydrogesterone
NIF
Ethynodiol acetate
33l - extensively bound to albumin and more specifically to sex
hormone binding globulin
Gestronol
NIF
Hydroxyprogesterone hexanoate
5l
Levonorgestrel
93-95% plasma bound
Megestrol Acetate
NIF
Medroxyprogesterone acetate
>20l, 94% is protein bound
Norethisterone
95% plasma bound
Norgestimate
NIF
Norgestrel
NIF
Progesterone
17-29l, 95-98% plasma protein bound
Metabolism
Dydrogesterone
Metabolised to glucuronide conjugates
Ethynodiol acetate
Metabolised in liver or gut wall to norethisterone and then to
sulphate and glucuronide conjugates.
Gestronol
NIF
Hydroxyprogesterone hexanoate
metabolised in liver
Levonorgestrel
Extensively metabolised by the liver
Megestrol Acetate
metabolised by liver to glucuronide conjugates
Medroxyprogesterone acetate
extensively metabolised in the liver
Norgestimate
NIF
Norgestrel
NIF
Norethisterone
Metabolised in the intestinal wall and liver
Progesterone
About 75% is metabolised presystemically to glucuronide
conjugates by the liver
Elimination
Dydrogesterone
60% is excreted via the urine within 72 hours. Only small amounts
are excreted via the faeces
Ethynodiol acetate
via urine and faeces
Gestronol
NIF
Hydroxyprogesterone hexanoate
NIF
Levonorgestrel
20-30% eliminated via the faeces and the rest via the urine
Megestrol Acetate
excreted as metabolites via the urine and faeces
Medroxyprogesterone acetate
mainly as conjugated metabolites in the faeces
Norethisterone
60% as metabolites in urine and faeces
Norgestrel
NIF
Progesterone
mainly as conjugates in the urine
Half-life
Dydrogesterone
about 6h
Ethynodiol acetate
about 25h
Gestronol
NIF
Hydroxyprogesterone hexanoate
2-11h, mean 4h
Levonorgestrel
10.26h
Megestrol Acetate
15-20h
Medroxyprogesterone acetate
about 30h
Norgestrel
NIF
Norethisterone
5 -12h
Progesterone
distribution - 3-6min; elimination - 19-95min
Breast Milk
Dydrogesterone
small quantities are have been measured in breast milk, but this
is unlikely to present any risk to the infant
Ethynodiol acetate
norethisterone concentration appears to reach a peak at about
4-8h after ingestion of ethynodiol acetate, small amounts of
norethisterone are excreted into breast milk, the concentration
being 10-20% of that in plasma
Gestronol
NIF, contraindicated in lactation
Hydroxyprogesterone hexanoate
contraindicated in lactation
Levonorgestrel
Approximately 0.1% of the daily dose passes into breast milk
Megestrol Acetate
Disease states being treated would usually contraindicate
breast-feeding
Medroxyprogesterone acetate
excreted into breast milk in concentrations similar to those in
plasma. No special precautions are advised.
Norgestrel
NIF
Norethisterone
daily oral dose of 350micrograms for contraception were reported
in one study to reduce milk volume somewhat but do not usually
affect volume or composition. Intramuscular injections of 200mg
each 8 weeks do not interfere with lactation. The plasma/milk
ratio of the heptanoate is about 10 and only 0.1% of the dose,
estimated as a maximum of 1.5micrograms daily, reaches the baby.
this is unlikely to affect the bay and is undetectable in the
baby's plasma at the time of the peak maternal plasma level.
There is a theoretical risk of all steroids interfering with
bilirubin conjugation, and maternal use of norethisterone should
probably be avoided whilst a baby has neonatal jaundice.
Progesterone
excreted in low concentrations, which are unlikely to have any
effect on the infant
TOXICOKINETICS
NIF
EPIDEMIOLOGY OF POISONING
In 1994, 2007 calls were made to UK NPIS centres about hormonal
contraceptive poisoning.
ADVERSE EFFECTS
General - Headaches/migraine, nausea, vomiting, breast changes, change
in weight, changes in libido, chloasma, breakthrough bleeding and
spotting, rash, depression, irregular cycle length, ocular changes,
increase in size uterine myofibromata and changes in carbohydrate,
lipid or vitamin metabolism. Rarely dizziness, hirsutism, haemorrhagic
eruption and colitis have been reported in users of progestogen-only
oral contraceptives
Megesterol - as above, rare reports of dyspnoea, heart failure,
hypertension, hot flushes, mood changes, cushingoid faces, tumour
flare (with or without hypercalcaemia), hyperglycaemia, alopecia and
carpel tunnel syndrome. Prolonged administration may cause urticaria.
Clinical and laboratory evidence of mild adrenal suppression
INTERACTIONS
Metabolism accelerated by rifamycins; increased plasma-cyclosporin
levels (inhibition of metabolism); aminoglutethimide reduces plasma
concentration of medroxyprogesterone
MECHANISM OF ACTION
Progestogens are synthetic compounds with actions similar to that of
progesterone. Progesterone is the main hormone secreted by the corpus
luteum. Large quantities are produced by the placenta during
pregnancy. It acts on the endometrium by converting the proliferative
phase induced by oestrogen to a secretory phase and preparing the
uterus to receive the fertilised ovum.
FEATURES OF POISONING
Acute
Ingestion
Toxicity is unlikely following an acute overdose. Occasionally there
may be nausea and vomiting. Withdrawal bleding may occur in females
even in pre-pubertal girls.
Chronic
Ingestion/Injection
Chronic or high dose therapy can result in jaundice, headache,
dizziness, oligomenorrhea or amenorrhea, congestion of the breasts and
decreased libido. Chronic toxicity may produce a thromboembolic state.
Pregnancy
During the pre-embryonic phase, which lasts until 17 days
post-conception, the 'all or nothing' concept is thought to apply.
During this period, cells damaged by a toxic insult, such as a drug
exposure, will be replaced by extra divisions of the remaining cells
which will then develop normally. If extensive damage occurs, failure
of implantation and spontaneous abortion may occur. Thus, if the
pregnancy is maintained, the risks to the fetus are likely to be no
greater than those for the general population.
The maternal administration of norethisterone to several species of
animals, including non-human primates, caused masculinisation of the
external female genitalia of the offspring but did not increase the
incidence of non-genital adverse fetal effects.1
There is no conclusive evidence of an association between progestogen
exposure in early pregnancy and non-genital malformations. Androgenic
hormones in human pregnancy have been associated with a small risk of
genital abnormalities when exposure occurs around about 6-7 weeks of
gestational age when the genitalia are beginning to develop.1-4
Approximately 1% of female fetuses exposed at this critical period of
development develop genital anomalies e.g. enlarged clitoris and
labial folds1,4. Internal genitalia and subsequent pubertal
development are not affected by norethisterone taken during pregnancy.
Male infants have an even smaller risk of genital anomalies, usually
hypospadias which can be treated surgically.
However, a recent meta-analysis of 14 studies involving 65,567 women
concluded that there was no association between 1st trimester exposure
to sex hormones generally, or to oral contraceptives specifically, and
external genital malformations.5
The use of norethisterone during any stage of pregnancy is
contra-indicated.
A number of congenital malformations, including cardiovascular,
central nervous system, multiple organ and limb defects, have been
reported in infants exposed to the drug in utero.1,2,3,4 However, the
role of norethisterone in the development of these anomalies has not
been established due to the influence of other factors such as alcohol
ingestion, cigarette smoking, concomitant drug therapy and maternal
obstetric history.1,3
There are three prospective follow-up reports from the European
Network of Teratology Information Services (ENTIS) following exposure
to progestogens during pregnancy. One patient had Norplant removed
after conception (details of timing of exposure not available), a
normal full term infant was born; there were two reports of exposure
to Depo-Provera, one woman had a dose at 1 week and 12 weeks of
gestation, a normal fullterm infant was born, the second woman was
exposed at 5 weeks of gestation and had an elective termination.
References
1. Gilstrap III LC, Little BB. Drugs and Pregnancy. Amsterdam:
Elsevier Science Publishing, 1992: 242-244
2. Folb PI, Dukes MNG (Eds). Drug Safety in Pregnancy. Amsterdam:
Elsevier Science Publishing, 1990: 273-281
3. Briggs CG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation.
4th ed. Baltimore: Williams and Wilkins, 1994
4. Schardein JL. Chemically Induced Birth Defects. 2nd ed. New York:
Marcel Dekker, 1993
5. Raman-Wilms L et al. Obs Gyn 1995; 85: 141-9
MANAGEMENT
Symptomatic treatment only is required.
Parents of prepubertal girls should be warned of the possibility of a
withdrawal bleed several days after ingestion.
ANALYSIS
NIF
PREVENTION OF POISONING
NIF
OTHER TOXICOLOGICAL DATA
Carcinogenicity
In a retrospective study of 5000 black women who received depot
medroxyprogesterone for contraception, no increased incidence in
breast, ovarian, or uterine corpus cancer was seen up to 13 years
later. (Liang et al 1993).
There is considerable evidence suggesting that after induction by
chemical carcinogens, sex hormones act as promoters of
heptocarcinogenesis.
Teratogenicity
There is no conclusive evidence of an association between progestogen
exposure in early pregnancy and non-genital malformations. Exposed
female infant have a small risk (approximately 1%) of clitoral
hypertrophy and fusion of the labioscrotal folds, when exposure occurs
during the critical period of genital development. These anomalies can
be corrected surgically. Male infants have an even smaller risk of
genital anomalies, usually hypospadias which can be treated
surgically.
Author
Helen Seymour, BPharm (Hons)
National Poisons Information Service (Newcastle Centre)
Regional Drug & Therapeutics Centre
Wolfson Building
Claremont Place
Newcastle upon Tyne
NE1 4LP
UK
This monograph was produced by the staff of the Newcastle Centre of
the National Poisons Information Service in the United Kingdom. The
work was commissioned and funded by the UK Departments of Health, and
was designed as a source of detailed information for use by poisons
information centres.
Peer review was undertaken by the Directors of the UK National Poisons
Information Service.
Last updated January 1997
REFERENCES
1. Martindale: The Extra Pharmacopoeia. 31st Edition. Reynolds JEF
(Ed.). Pharmaceutical Press 1996.
2. Therapeutic Drugs. Dollery C. (Ed.). Churchill Livingstone 1991.
3. ABPI Compendium of Data Sheets and Summaries of Product
Characteristics. Datapharm Publications Ltd. 1996-97.
4. British National Formulary. Number 32 (September 1996). British
Medical Association and Royal Pharmaceutical Society.
5. Poisindex Systemœ, Micromedex, Inc., Denver Colorado, Edition
Expires 31.12.96.
6. National Teratology Information Service.
7. European Commission; Poison centres: Collection of the annual
reports 1994, Analysis and synthesis, Final Report 31.8.96.