Warning - Human health risks
Most drugs with reproductive effects have the same actions in people. For example, prostaglandins will lyse corpora lutea, cause uterine contractions and therefore have the potential to cause abortion in pregnant women. Progestagens can cause cessation of cyclicity in women.
Some drugs have potentially life threatening effects in people. A prime example is prostaglandin F2α and analogues. Prostaglandins have a more severe effect on the respiratory tract in people than in many animals, causing bronchoconstriction and respiratory distress. People with respiratory disease (including asthma) need to be particularly careful. These drugs can be absorbed across intact skin in large enough quantities to cause major problems.
You need to know the physiology of reproduction in order to make sense of what these drugs do.
Testosterone is the natural hormone. It is used in as various esters. Other androgens (usually described as anabolic steroids) include: boldenone, stanozolol, nandrolone, methandriol, ethylestrenol, etc
Natural sources are: gonads - testes primarily, ovaries (mainly as a precursor to oestrogens), placenta and adrenal gland.
Therapeutic uses
male sexual behaviour
negative feedback on gonadotropins
anabolic effects - appetite stimulant, RBC production, nitrogen retention etc
epidermal effects - sex hormone responsive dermatoses in small animals
urinary bladder urethral muscle maintenance in male castrates
Adverse effects
Masculinization and aggressive behaviour
negative feedback on gonadotopins (cessation of cyclicity and of spermatogenesis)
chronic use of high doses and different drugsin people has been associated with severe effects on general health including cardiovacular disease, mental disorders, neolpasia etc.
Delmadinone is a progestogen which is used as an antiandrogen.
Natural source is the anterior pituitary gland.
Currently made by extracting hormone from anterior pituitary glands mostly from sheep or pigs (oFSH = ovine, pFSH = porcine). All products are contaminated to some extent with other hormones such as LH. Newer techniques have resulted in greater purity. LH contamination is generally considered to be undesirable since it makes the response of the ovary more unpredictable. Synthetic FSH products are being developed. Biological half life is about 6 hours and therefore twice daily injections required to achieve results.
Therapeutic uses
stimulation of follicle growth and development for oestrus induction and superovulation.
Adverse effects
excessive stimulation of follicle production resulting in ovarian cysts, endometrial hyperplasia, hyper-oestrogenism.
Natural source is the anterior pituitary gland. LH products are also made from pituitary extracts and are generally available only for research purposes. Other products are used commercially for their LH like actions (hCG and GnRH).
Therapeutic uses
Induction of ovulation
Formerly known as Pregnant Mare Serum Gonadotropin (PMSG) and still marketed under this name in some regions. The natural source is endometrial cups in pregnant mares between days 40-120 of pregnancy. Produced commercially by extracting eCG from serum of pregnant mares or ponies.
Therapeutic uses
In the mare, eCG has a primarily LH like action. It binds to LH receptors and results in resurgence of the primary CL of pregnancy and formation of secondary CLs. It has no application in equine reproduction because such massive doses appear to be required to have any effect at all in mares. In other species, eCH binds to both LH and FSH receptors and has a long half life and therefore has become useful in stimulating the development of follicles and ovulation. It is widely used in domestic species other than the mare (sheep, cow, pig) to stimulate development of multiple follicles (superovulation) and to induce oestrus and ovulation in non-cycling animals (pigs).
Long half life (72 hours) and therefore used as a single injection.
Adverse effects
eCG has a long duration of action and therefore even a single dose can result in excessive stimulation of ovarian follicular development, resulting in cystic follicles, poor superovulatory response, hyperoestrogenism. Recently researchers have developed an anti-eCG antibody and have administered it 2 days after eCG to stop the adverse effects associated with its prolonged activity. This appears to make the product more effective as a superovulatory drug for domestic species.
Comes from human early blastocyst and placenta - appears in early pregnancy. Commercial product made from the urine of pregnant women.
Actions
LH like effect primarily and involved in women in CL support and pregnancy maintenance. In other species it is used for its LH effect primarily, for example ovulation induction, challenge testing, treatment of cryptorchidism.
hCG is a relatively large molecule and is capable of inducing an antigenic response in animals since it represents foreign protein.
Comes from the hypothalamus. GnRH is a very small molecule (decapeptide) which is easily synthesized and numerous synthetic formulations are available. There is no risk of antibody stimulation and therefore very safe to use. It appears to be replacing hCG in most applications for these reasons.
Actions
Stimulation of LH and FSH release and therefore stimulation of ovarian and testicular activity.
induction of cyclicity and ovulation (cystic ovaries in cows, ovulation in all species)
increased spermatogenesis ?
increased libido?
challenge or diagnostic testing.
Injectable products have been available for years. Recently a biodegradable implant was released for use in horses to cause ovulation.
Oestradiol 17-β is the natural hormone; oestradiol esters such as the cypionate or benzoate are often injected. Oestradiol is rapidly metabolised when given by mouth, so ethinyloestradiol is used orally. Stilboestrol (diethylstilboestrol, DES) is no longer available in NZ.
Natural sources are ovarian follicle and corpus luteum, testes, placenta, adrenal gland.
Therapeutic uses
behavioural receptivity
embryotoxic effects
anabolic effects (ruminants)
feedback effects on gonadotropin release
increased resistance of the female genital tract to infection
mammary gland development
abortion
maintenance of normal urethral muscle tone in small animals
epidermal effects - sex hormone responsive dermatoses in small animals
Adverse effects
feminization
behavioural receptivity
mammary gland development
abortion
negative feedback effects on gonadotropins (ovarian cysts, cessation of cyclicity)
increased uterine gland activity (CEH)
bone marrow suppression and aplastic anaemia
carcinogenic and teratogenic
Antioestorgens such as tamoxifen and oestrogen production inhibitors such as letrozole are sometimes used in women but are expensive.
ProstaglandinF2α (dinoprost - not to be confused with dinoprostone = PGE2) is produced by all tissues. Numerous synthetic analogues, such as cloprostenol, luprostiol (= prostianol) and etiproston are used as well as the natural compound.
Therapeutic uses
corpus luteum regression - oestrus synchronization, abortion, induced parturition
smooth muscle contraction - uterus
cervical relaxation
Adverse effects
corpus luteum regression as above (abortion)
Smooth muscle contraction - vasoconstriction, bronchoconstriction, salivation, sweating, vomiting, diarrhoea, abdominal pain, micturition, pruritis, erythema, ataxia, increased vocalization, tail movement, tachycardia, fever, anxiety, pupillary dilation or constriction.
Signs in horses are mainly sweating and abdominal pain.
Side effects in animals generally appear within minutes of administration of drug and last for 15-30 minutes. Animals become accustomed to the drugs with repeated usage and side effects tend to diminish in intensity and range.
People: women of child bearing age, pregnant women, people with asthma or other respiratory complaints must use extreme caution when handling PGF2?. Prostaglandin analogues are readily absorbed through the skin (wear gloves) or as a vapour via the respiratory tract (be careful not to spray it around).
Progesterone is the natural hormone; there are numerous synthetic progestagens: altrenogest (allyltrenbolone), megestrol, proligestone, medroxyprogesterone, hydroxyprogesterone, flugestone and norgestomet
Natural sources are the ovary and corpus luteum, placenta in some species, adrenal gland.
Therapeutic uses
feedback effects on gonadotropins (largely negative)
inhibits expression of oestrus behaviour
pregnancy maintenance
mammary gland development (together with oestrogens)
CNS calming effect
Thermogenic (body temp drop used as a predictor of impending parturition)
Adverse effects
increased risk of CEH and pyometra in bitch and queen, especially when coupled with increased oestrogens.
increased appetite and weight gain
decreased activity
personality changes
mammary gland enlargement, milk production and neoplasia
increased growth hormone secretion - acromegaly, protein synthesis and growth; insulin resistance, increased blood glucose levels, pancreatic exhaustion and eventually diabetes mellitus.
adrenocortical suppression: mainly seen in cats on progestagens with adrenal atrophy and Addison’s syndrome which may occur within 1-2 weeks of beginning therapy in cats.
