From Wikipedia, the free encyclopedia
Drug
An antigonadotropin is a
drug which suppresses the activity and/or downstream effects of one or both of the
gonadotropins ,
follicle-stimulating hormone (FSH) and
luteinizing hormone (LH). This results in an inhibition of the
hypothalamic-pituitary-gonadal (HPG) axis , and thus a decrease in the levels of the
androgen ,
estrogen , and
progestogen
sex steroids in the body. Antigonadotropins also inhibit
ovulation in women and
spermatogenesis in men. They are used for a variety of purposes, including for the
hormonal birth control , treatment of
hormonally -sensitive
cancers , to delay
precocious puberty and
puberty in
transgender youth , as a form of
chemical castration to reduce the
sex drives of individuals with
hypersexuality or
pedophilia , and to treat estrogen-associated conditions in women such as
menorrhagia and
endometriosis , among others. High-dose antigonadotropin therapy has been referred to as medical castration .
The best-known and widely used antigonadotropins are the
gonadotropin-releasing hormone (GnRH)
analogues (both
agonists and
antagonists ).
[1] However, many other drugs have antigonadotropic properties as well, including compounds acting on sex steroid hormone receptors such as progestogens, androgens, and estrogens (due to
negative feedback on the HPG axis),
[2]
[3] as well as steroid
synthesis inhibitors such as
danazol and
gestrinone .
[4]
[5] Since progestins have relatively little effect on
sexual differentiation compared to the other sex steroids,
potent ones such as
cyproterone acetate ,
medroxyprogesterone acetate , and
chlormadinone acetate are often used at high doses specifically for their antigonadotropic effects.
[2]
[6]
[7]
Danazol ,
gestrinone , and
paroxypropione have all been classified specifically as antigonadotropins.
[8]
Prolactin has antigonadotropic effects and
hyperprolactinemia can cause
hypogonadism .
[9]
[10]
Opioids have antigonadotropic effects and can reduce luteinizing hormone and testosterone levels in men.
[11]
[12]
[13] A 2015
systematic review and
meta-analysis found that opioid therapy decreased testosterone levels in men by about 165 ng/dL (5.7 nmol/L) on average, which was a reduction in testosterone level of almost 50%.
[11] In contrast to opioids,
opioid antagonists , like
naltrexone , have
progonadotropic effects, and can increase luteinizing hormone and testosterone levels.
[14]
See also
References
^ Jonathan S. Berek; Emil Novak (2007).
Berek and Novak's Gynecology . Lippincott Williams & Wilkins. p. 212.
ISBN
978-0-7817-6805-4 . Retrieved 29 May 2012 .
^
a
b de Lignières B, Silberstein S (April 2000). "Pharmacodynamics of oestrogens and progestogens". Cephalalgia: An International Journal of Headache . 20 (3): 200–7.
doi :
10.1046/j.1468-2982.2000.00042.x .
PMID
10997774 .
S2CID
40392817 .
^ Gooren L (October 1989). "Androgens and estrogens in their negative feedback action in the hypothalamo-pituitary-testis axis: site of action and evidence of their interaction". Journal of Steroid Biochemistry . 33 (4B): 757–61.
doi :
10.1016/0022-4731(89)90488-3 .
PMID
2689784 .
^ Jonathan S. Berek; Emil Novak (2007).
Berek and Novak's Gynecology . Lippincott Williams & Wilkins. p. 1167.
ISBN
978-0-7817-6805-4 . Retrieved 29 May 2012 .
^ Singh H, Jindal DP, Yadav MR, Kumar M (1991). "Heterosteroids and drug research". Progress in Medicinal Chemistry . 28 : 233–300.
doi :
10.1016/s0079-6468(08)70366-7 .
ISBN
9780444812759 .
PMID
1843548 .
^ Bercovici JP (September 1987). "[Progestational contraception]". La Revue du Praticien (in French). 37 (38): 2277–8, 2281–4.
PMID
3659794 .
^ Chassard D, Schatz B (2005). "[The antigonadrotropic activity of chlormadinone acetate in reproductive women]". Gynécologie, Obstétrique & Fertilité (in French). 33 (1–2): 29–34.
doi :
10.1016/j.gyobfe.2004.12.002 .
PMID
15752663 .
^ George W.A. Milne (8 May 2018).
Drugs: Synonyms and Properties: Synonyms and Properties . Taylor & Francis. pp. 674–.
ISBN
978-1-351-78989-9 .
^ Bernard V, Young J, Binart N (June 2019). "Prolactin - a pleiotropic factor in health and disease". Nat Rev Endocrinol . 15 (6): 356–365.
doi :
10.1038/s41574-019-0194-6 .
PMID
30899100 .
S2CID
84846294 .
^ Saleem M, Martin H, Coates P (February 2018).
"Prolactin Biology and Laboratory Measurement: An Update on Physiology and Current Analytical Issues" . Clin Biochem Rev . 39 (1): 3–16.
PMC
6069739 .
PMID
30072818 .
^
a
b Bawor M, Bami H, Dennis BB, Plater C, Worster A, Varenbut M, Daiter J, Marsh DC, Steiner M, Anglin R, Coote M, Pare G, Thabane L, Samaan Z (April 2015).
"Testosterone suppression in opioid users: a systematic review and meta-analysis" . Drug Alcohol Depend . 149 : 1–9.
doi :
10.1016/j.drugalcdep.2015.01.038 .
PMID
25702934 .
^ Coluzzi F, Billeci D, Maggi M, Corona G (December 2018).
"Testosterone deficiency in non-cancer opioid-treated patients" . J Endocrinol Invest . 41 (12): 1377–1388.
doi :
10.1007/s40618-018-0964-3 .
PMC
6244554 .
PMID
30343356 .
^ Smith HS, Elliott JA (July 2012). "Opioid-induced androgen deficiency (OPIAD)". Pain Physician . 15 (3 Suppl): ES145–56.
PMID
22786453 .
^ Tenhola H, Sinclair D, Alho H, Lahti T (February 2012). "Effect of opioid antagonists on sex hormone secretion". J Endocrinol Invest . 35 (2): 227–30.
doi :
10.3275/8181 .
PMID
22183092 .
S2CID
31583157 .
External links
GnRH modulators (incl.
analogues )
Gonadotropins
Others (indirect)
Progonadotropins
Antigonadotropins
Sex steroid agonists (via negative feedback on the
HPG axis ):
Androgens /
anabolic steroids (e.g.,
testosterone ,
nandrolone esters ,
oxandrolone )
D2 receptor
antagonists (
prolactin releasers ) (incl.,
domperidone ,
metoclopramide ,
risperidone ,
haloperidol ,
chlorpromazine ,
sulpiride )
Estrogens (incl.,
bifluranol ,
estradiol ,
estradiol esters ,
ethinylestradiol ,
diethylstilbestrol ,
paroxypropione )
Progestogens (incl.
progestins , e.g.,
chlormadinone acetate ,
cyproterone acetate ,
hydroxyprogesterone caproate ,
gestonorone caproate ,
medroxyprogesterone acetate ,
megestrol acetate )
GnRH Tooltip Gonadotropin-releasing hormone receptor
Gonadotropin
LH/hCG Tooltip Luteinizing hormone/choriogonadotropin receptor
FSH Tooltip Follicle-stimulating hormone receptor