Progestogens

By | 2011-08-18

Progestogens are steroids that mimic the effects of progesterone and thus prepare and maintain the female reproductive tract for implantation and pregnancy. They cause development of the mammary glands to the point of lactation. Progestogens exert a negative feedback on the hypothalmic-pituitary axis suppressing the secretion of gonadotrophins, and thereby cyclical ovarian activity, which normally results in oestrus and ovulation. In male animals, progestogens reduce testosterone production by the same action.

In mares, cows, ewes, does, and sows, progestogens are used to synchronise oestrus in groups of animals or enable the occurrence of oestrus to be predicted. Administration of a progestogen for 10 to 14 days will suppress cyclical ovarian activity and oestrus. Longer periods of administration may cause decreased fertility. On removal of the progestogen source, the negative feedback on the pituitary and the hypothalamus is removed and oestrus with subsequent ovulation occurs. This facilitates the use of artificial insemination and stud males. This treatment may also be used in individual animals.

Altrenogest is administered in the feed to mares, gilts, and sows. In sows and gilts, oestrus occurs 5 to 7 days after the last day of treatment. Flugestone and medroxyprogester-one are administered as intravaginal sponges in ewes and does . On withdrawal of the sponge, serum gonadotrophin may be administered as a single dose, the dose varying according to breed and times of administration. This method is used to advance the time of onset of cyclical ovarian activity. Rams are introduced into the flock 48 hours after removal of sponges.

Progesterone is administered to cattle by using a progesterone-releasing intravaginal device (Eazi-Breed CIDR, see also Prid). Prostaglandin F2alpha or an analogue may be administered before removal of the progesterone device to improve the accuracy of synchronisation. Progestogens may be used to stimulate the onset of cyclical ovarian activity in anoestrus mares, cows, ewes, does, and sows. Their effect is evident following withdrawal. Animals are usually mated at the synchronised oestrus, although ewes may be mated at the second oestrus after removal of a progestogen-impregnated sponge. In dogs and cats, medroxyprogesterone, megestrol, and proligestone are used to postpone or suppress oestrus. For guidance, medical treatment (rather than surgical intervention) may be used for prevention of oestrus in animals that are poor surgical risks for ovariohysterectomy and animals from which litters are temporarily not desired. In cats, eosinophilic granuloma and ‘miliary dermatitis’ (crusting dermatosis) are responsive to progestogens because they have a glucocorticoid-like anti-inflammatory effect, although their use for dermatitis is contra-indicated. Prolonged administration of megestrol acetate may lead to side-effects (see below), and oral corti-costeroids or preferably elimination of the causative agent are recommended for the treatment of ‘miliary dermatitis’. Megestrol and medroxyprogesterone may be given for behavioural problems in dogs. Delmadinone is used in the treatment of prostatic hypertrophy, prostatic carcinoma, and perianal tumours. It improves behaviour in some forms of aggression, nervousness, and hypersexuality.

Hydroxyprogesterone has actions similar to other progestogens and has been used to prevent recurrent abortion. Progestogens should be used with caution. All synthetic progestogens differ in their pharmacological profiles and their capacities to produce side-effects in different animal species. For example, although some progestogens may be used to inhibit or retard the growth of certain oestrogen-dependent mammary tumours and treat pseudopregnancy in bitches, it is known that other progestogens can cause or aggravate these conditions.

Progestogens stimulate the proliferative and secretory activity of the uterine endometrium leading to cystic endometrial hyperplasia, mucometra, or pyometra. Therefore, progestogens should not be administered to animals with a history of vaginal discharge or reproductive abnormalities, sexually immature animals, or dogs and cats intended for breeding. When used for suppression of oestrus in dogs and cats, animals should be allowed to have a normal cycle every 18 to 24 months.

Progestogens antagonise the hypoglycaemic effects of insulin and therefore should not be given to diabetic animals. The possibility of pre-existing disease should be considered when treating patients requiring long-term progestogen therapy. Some progestogens, such as megestrol acetate, may induce profound adrenal cortical suppression and possibly hypoadrenacortical syndrome on rapid withdrawal. Progestogens may induce acromegaly in entire bitches. Subcutaneous injection of progestogens may cause hair discoloration and localised alopecia and thinning of the skin. Injection should be given in an inconspicuous area, such as the inner fold of the flank or medial aspect of the thigh. Some patients given progestogens may develop a tendency for obesity or a change in temperament.

Preparations containing progestogens should be handled with care, particularly by women of child-bearing age. Impervious gloves and suitable protective overalls should be worn when in contact with such preparations.

ALTRENOGEST

Indications. See under Dose

Contra-indications. Male animals, immature animals, animals with uterine infection

Warnings. Partly consumed medicated feed should be safely destroyed and not given to any other animal; correct dose must be given because underdosing may lead to formation of cystic ovaries. Care must be taken to avoid any contact between preparations of the drug and women of child-bearing age; the manufacturer recommends that women of child-bearing age should not be associated with the use of these preparations; women with irregular menstrual periods after exposure to these preparations should consult their doctor; operators should wear protective clothing when handling the product

Dose: By addition to feed.

Horses: anoestrus (not deep anoestrus), suppression of prolonged oestrus during the transitional phase before the resumption of normal cyclical ovarian activity, 44 micrograms/kg daily for 10 days

Suppression and control of oestrus in cycling mares, 44 micrograms/kg daily for 15 days

Pigs: (gilts) synchronisation of oestrus, 20 mg daily for 18 days; (sows) synchronisation of oestrus, 20 mg daily for 3 days, starting on day of weaning

Prescription-only medicine: Regumate Equine (Intervet) UK

Oral solution, for addition to feed, altrenogest 2.2 mg/mL, for horses

Withdrawal Periods. Should not be used in horses intended for human consumption

Prescription-only medicine: Regumate Porcine (Janssen) UK

Oral suspension, for addition to feed, altrenogest 20 mg/unit dose, for pigs; metered-dose applicator (1 unit dose = 5 mL)

Withdrawal Periods.

Pigs: slaughter 15 days

DELMADINONE ACETATE

Indications. Treatment of hypersexuality, relief of prostatic hypertrophy, perianal (circumanal, hepatoid) gland tumours; certain behavioural problems

Contra-indications. Concurrent administration of other progestogens

Side-effects. Transient reduction in fertility and libido; transient increased appetite, polydipsia and polyuria; discoloration of hair at injection site

Warnings. Clinical response to treatment is 2-4 days

Dose:

Dogs, cats: by subcutaneous or intramuscular injection, 1-2 mg/kg depending on the weight of the animal and severity of the condition, repeat dose after 8 days if no improvement. Repeat dose every 3-4 weeks in animals showing improvement

Prescription-only medicine: Tardak (Pfizer) UK

Injection, delmadinone acetate 10 mg/mL, for dogs, cats

FLUGESTONE ACETATE

(Flurogestone acetate)

Indications. See under Dose

Contra-indications. Ewe lambs, ewes not previously bred

Warnings. Operators should wear protective gloves when handling sponges; the physical and nutritional state of the flock must be good for use in non-breeding season

Dose: Sheep, goats: synchronisation of oestrus during the breeding season, by intravaginal administration, one 30-mg sponge. Remove after 14 days Induction of oestrus and ovulation during non-breeding season, advancement of breeding season, by intravaginal administration, one 30-mg sponge. Remove after 12 days, followed within 6 hours by serum gonadotrophin, by subcutaneous or intramuscular injection, 500 units

Prescription-only medicine: Chronogest (Intervet) UK

Vaginal sponge, flugestone acetate 30 mg, for sheep

Disinfectant

Liquid concentrate, benzalkonium bromide 5%. To be diluted before use

Dilute 1 volume in 90 volumes water

Withdrawal Periods.

Sheep: slaughter 14 days after removal of sponge, should not be used in sheep producing milk for human consumption

Note. After each application, the sponge applicator should be wiped clean and placed in the supplied disinfectant. Do not use alcohols, cresols, phenols, sheep dip or other disinfectants

MEDROXYPROGESTERONE ACETATE

Indications. See under Dose; behaviour modification

Contra-indications. Use in bitches primarily intended for breeding purposes, use before first oestrus, pregnant animals, previous history of genito-urinary disease, persistant or abnormal vaginal discharge, irregular oestrus or nymphomania, pseudopregnancy, mammary tumours, pro-oestrus, oestrus, or metoestrous stage of oestrous cycle; diabetes mellitus; use in maiden ewes, ewes with vaginal discharge or just after abortion

Side-effects. Thinning of skin, thinning and discoloration of hair at injection site; mammary hyperplasia or nodules; weight gain; cystic endometrial hyperplasia

Warnings. Injection should be given in inconspicuous site; owners should be warned that return to oestrual cycling is variable after long-term treatment; operators should wear protective gloves when handling sponges and take care to avoid damaging the vagina; the sponge should be removed and ewes examined if there is excessive straining after insertion or blood on the applicator; all sponges should be removed after 17 days

Dose:

Sheep, goats : synchronisation of oestrus, by intravaginal administration, one 60-mg sponge. Remove after 13-17 days

Induction of oestrus and ovulation during non-breeding season, advancement of breeding season, by intravaginal administration, one 60-mg sponge. Remove after 13-17 days and by subcutaneous or intramuscular injection, serum gonadotrophin, 300-750 units, given at time of sponge removal (dose dependent on breed and time interval to normal breeding)

Dogs: prevention of oestrus, by subcutaneous injection, 50 mg given in anoestrus. Repeat after 6 months

Prescription-only medicine: Promone-E (Pfizer) UK

Injection, medroxyprogesterone acetate 50 mg/mL, for dogs

Prescription-only medicine: Veramix Sheep Sponge (Pfizer) UK

Vaginal sponge, medroxyprogesterone acetate 60 mg, for sheep

Withdrawal Periods.

Sheep: slaughter 14 days after removal of sponge, should not be used in sheep producing milk for human consumption

Note. After each application, the sponge applicator should be wiped clean and washed in water containing a suitable disinfectant such as cetrimide 0.5-1.0%. Do not use alcohols, cresols, phenols, or similar disinfectants

MEGESTROL ACETATE

Indications. See notes above and under Dose; behaviour modification

Contra-indications. Diabetes mellitus; male dogs intended for breeding

Side-effects. Rarely excess libido; occasionally lethargy, weight gain; mammary hypertrophy

Warnings. Not more than 2 courses of treatment for postponement of oestrus should be given per 12-month period in bitches; owners should be warned that the time interval to the subsequent oestrus is variable

Dose: By mouth.

Dogs. Females: prevention of oestrus, 2 mg/kg daily for 8 days or 2 mg/kg daily for 4 days then 500 micrograms/kg daily for 16 days, given at pro-oestrus Postponement of oestrus, 500 micrograms/kg daily for up to 40 days given in anoestrus and 7-14 days before postponement is required

Males: behavioural problems, see section 6.11.11

Cats: miliary dermatitis, eosinophilic granuloma, 2.5-5.0 mg every 2-3 days until lesions regress then once weekly until satisfactory response. Then maintenance dose of 2.5 mg every 7-14 days if required

Females: prevention of oestrus, 5 mg daily for 3 days given in pro-oestrus

Postponement of oestrus, 2.5 mg once weekly for up to 30 weeks and given in anoestrus

Prescription-only medicine: Ovarid (Schering-Plough) UK

Tablets, scored, megestrol acetate 5 mg, 20 mg, for dogs, cats

PROGESTERONE

Indications. See under Dose

Contra-indications.

Side-effects. See notes above

Dose:

Cattle: induction of oestrus and ovulation in anoestrus, by intravaginal administration, 1 device. Remove after 7-12 days

Synchronisation of oestrus and ovulation, by intravaginal administration, 1 device. Remove after 7-12 days and administration of prostaglandin F2alpha (see site for dosage) at time of removal, or at any time from 6 days after insertion. GnRH (buserelin and gonadorelin, section 8.1.2) may be used in conjunction with intravaginal progesterone to stimulate follicular growth

Prescription-only medicine: Eazi-Breed CIDR (ART) UK

Intravaginal device, progesterone 1.9 g, for cattle

Withdrawal Periods.

Cattle: slaughter 6 hours after removal of device, milk withdrawal period nil

PROLIGESTONE

Indications. See notes above and under Dose

Contra-indications. Use in bitches treated previously with oestrogens or progestagens for pseudopregnancy

Side-effects. Thinning of skin, thinning and discoloration of hair at injection site; mammary hyperplasia; transient weight gain and lethargy; cystic endometrial hyperplasia

Warnings. Injection should be given in inconspicuous site; occasional anaphylactic reaction; use with caution in diabetic animals; for suppression of oestrus bitches, should be in early pro-oestrus when treated; bitches may accept male for a few days after treatment and contact with males should be prevented until signs of oestrus have regressed

Dose: By subcutaneous injection.

Dogs: permanent postponement of oestrus, 10-33 mg/kg (larger animals receive proportionally lower doses), repeat after 3, 4, and 5 months

Temporary postponement of oestrus, suppression of oestrus at onset of pro-oestrus, 10-33 mg/kg as a single dose Pseudopregnancy, 10-33 mg/kg. May repeat after 1 month if required

Cats: postponement and suppression of oestrus, 100 mg Miliary dermatitis, 33-50 mg/kg, repeat every 4 months, or more frequently depending on response

Ferrets: to prevent problems associated with prolonged oestrus, 50 mg/animal

Prescription-only medicine: Delvosteron (Intervet) UK

Injection, proligestone 100 mg/mL, for dogs, cats, ferrets