Antigonadotropic agents suppress the effects of the gonadotropins FSH and LH through inhibition of the hypothalamic-pituitary-gonadal axis, thereby decreasing sex steroid hormone levels. They are used to treat cancers, delay puberty, reduce sex drive through chemical castration, and treat estrogen-associated conditions in women. The most widely used antigonadotropins are gonadotropin-releasing hormone agonists and antagonists, which suppress FSH and LH through interaction with GnRH receptors in the pituitary gland. Other classes of antigonadotropic agents include progestogens, antiandrogens, estrogens, and steroid synthesis

1. ANTIGONADOTROPIC
AGENTS
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2. WHAT ARE THEY?
•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).
• 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.

3. USES
• Antigonadotropins are used for a variety of purposes, including:
• for the treatment 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 (namely males)
with hypersexuality or pedophilia
• and to treat estrogen-associated conditions in women
such as menorrhagia and endometriosis.
• These medications can be administered intranasally, by injection, or by
implant. Injectables have been formulated for daily, monthly, and quarterly
use; and implants can last from 1 to 12 months.

4. ANTIGONADOTROPINS
• The most well-known and widely used antigonadotropins are
the gonadotropin-releasing
hormone (GnRH) analogues (both agonistsand antagonists).
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), as well as
steroid synthesis inhibitors such as danazol and gestrinone.
Some antigonadotropins have a multimodal action, such as
cyproterone acetate, which exerts its effects via acting as
an antiandrogen, progestin, and steroid synthesis
inhibitor. Since progestins have relatively little effect on sexual
differentiation compared to the other sex steroids, potent ones
such as medroxyprogesterone acetate and chlormadinone

5. GONADOTROPIN RELEASING HORMONE
AGONISTS
• is a synthetic peptide modeled after the
hypothalamic neurohormone GnRH that interacts with
the gonadotropin-releasing hormone receptor to elicit
its biologic response which is the release of
the pituitary hormones FSH and LH leading to a surge.
• Examples of GnRH agonists are:
• triptorelin (Trelstar La)
• leuprolide (Lupron Depot)
• goserelin (Zoladex)

6. .
• Side effects of the GnRH agonists are signs and symptoms
of hypoestrogenism, including hot flushes, headaches, and osteoporosis.
In patients under long-term therapy, small amounts of estrogens could
be given back (“add-back regimen”) to combat such side effects and to
prevent bone wastage. Generally, long-term patients, both male and
female, tend to undergo annual DEXA scans to appraise bone density.
• There is also a report that GnRH agonists used in the treatment of
advanced prostate cancer may increase the risk of heart problems by 30%
• Agonists do not quickly dissociate from the GnRH receptor. As a result,
initially there is an increase in FSH and LH secretion (so-called "flare
effect").
• However, after about ten days, a profound hypogonadal effect (i.e.
decrease in FSH and LH) is achieved through receptor downregulation by
internalization of receptors. Generally this induced and

7. GONADOTROPIN RELEASING HORMONE
ANTAGONISTS
• GnRH antagonists competitively and reversibly bind to GnRH
receptors in the pituitary gland, blocking the release
of luteinising hormone (LH) and follicle-stimulating
hormone(FSH) from the pituitary. In men, the reduction in LH
subsequently leads to rapid suppression of testosterone release
from the testes; in women it leads to suppression of
estrogen release from the ovaries.
• Unlike the GnRH agonists, which cause an initial stimulation of
the hypothalamic-pituitary-gonadal axis (HPGA), leading to a
surge in testosterone or estrogen levels, GnRH antagonists
have an immediate onset of action, rapidly reducing sex

8. DRUGS
• Currently approved GnRH antagonists include the following:
• Cetrorelix
• Ganirelix
• Abarelix
• Degarelix
• SIDE EFFECTS: As with all hormonal therapies, GnRH antagonists are
commonly associated with hormonal side effects such as hot
flushes, headache, nausea and weight gain. When used in fertility
treatment they can also be associated with abdominal pain and ovarian
hyperstimulation. Subcutaneously administered agents are also
associated with injection-site reactions and abarelix has been linked with
immediate-onset systemic allergic reactions.

9. PROGESTOGENS• Progestogens, similarly to the androgens and estrogens through their own
respective receptors, inhibit the secretion of the gonadotropins follicle-
stimulating hormone (FSH) and luteinizing hormone (LH) via activation of the
progesterone receptor. This effect is a form of negative feedback on
the hypothalamic-pituitary-gonadal (HPG) axis that the body uses to prevent sex
hormone levels from becoming too elevated. Accordingly, progestogens, both
endogenous and exogenous (i.e., progestins), have antigonadotropiceffects, and
progestins in sufficient amounts can markedly suppress the body's normal
production of progestogens, androgens, and estrogens, as well as, in theory,
neurosteroids. As such, some of the more potent progestins,
including chlormadinone acetate, cyproterone acetate, medroxyprogesterone
acetate, and megestrol acetate are sometimes used to suppress sex hormone
levels in a variety of androgen and estrogen-associated conditions. Examples of
indications include treating sex hormone-sensitive cancers (e.g., breast cancer),
suppressing precocious puberty and puberty in transgender youth, and
reducing sex drive in sex offenders and individuals with

10. ANTIANDROGENS AND ESTROGENS
• Since estrogen circulating in the blood can negatively feed-
back to reduce circulating levels of FSH and LH, most oral
contraceptives contain a synthetic estrogen, along with a
synthetic progestin.
• Antiandrogens are used to treat an array of medical conditions
that are dependent on the androgen pathway. Antiandrogens
are often prescribed for men with prostate cancer,benign
prostatic hyperplasia, hypersexuality, and male contraception,
and for men undergoing gender reassignment. For women,
antiandrogens are often prescribed for severe cases
of acne, amenorrhea, seborrhea, hirsutism, androgenic
alopecia, hidradenitis suppurativa, and hyperandrogenism.

11. STEROID SYNTHESIS INHIBITORS
• Danazol - drug , a synthetic androgen
• Antigonadotropnym agent is a synthetic androgen derived
from ethisterone . It inhibits production of
pituitary gonadotropic hormones LH and FSH levels in men and
women. In women, it inhibits the activity of the ovaries ,
inhibits ovulation , causes atrophy of the endometrium . Action
reversible, deprived of estrogen or progestin action in high doses has
a weak androgenic activity with concomitant anabolic
effect. With Endometriosis affects both normal and ectopic
endometrial tissue, resulting in its inactivation, and
atrophy.Reduces pain , associated endometriosis causes regressive
changes of endometrial lesions. It exerts immunosuppressive effect
and inhibits the proliferation of lymphocytes in vitro . Significantly
reduces the level of Ig and autoantibody production in patients with
endometriosis. With fibrocystic breast promotes partial or complete
disappearance of nodular seals and complete relief of pain. Clinical
efficacy in hereditary angioedema , possibly due to an increase in the
content of inhibitor of esterase C1 (congenital deficiency of which is

12. CONTRAINDICATIONS AND SIDE EFFECTS
• Hypersensitivity , pregnancy ,
during lactation , porphyria (increased activity of
"liver" transaminases ), liver and / or kidney failure , chronic
heart failure , thromboembolism , androgen tumor , vaginal
bleeding (of unknown origin).
• SIDE EFFECTS: "Vulgar" eels , hypersecretion of the sebaceous
glands , fluid retention, hirsutism , "tides" of blood to the skin
of the face, profuse perspiration, reducing the size of the
breasts, deepening of voice, weight gain, vaginitis , violation
of spermatogenesis , virility syndrome , nausea , dizziness, ,
emotional lability, spasm of skeletal muscles, headache,
increased intracranial pressure , lumbodynia , paresthesia ,
sleep disorders, disorders bleeding in patients

13. STEROID SYNTHESIS INHIBITORS
• Gestrinone is a synthetic steroid with
mixed progestogen and antiprogestogen (i.e., partial agonist)
effects, and also has some mild androgenic activity. It is
marketed under the names Dimetriose, Dimetrose,
and Nemestran, as a treatment for endometriosis.
• Its mechanism of action consists of suppression of the release
of pituitary gonadotropins. Gestrinone also interacts with the
endometrium, inhibiting its growth. The inhibition is the result
of gestrinone's interaction with the androgen receptor; this is
also the reason for androgenic side effects. Gestrinone has
been shown to interact with the estrogen receptor,
the androgen receptor, and the progesterone receptor.

14. .
• The drug is contraindicated in pregnancy, during lactation, and in
patients with severe cardiac, renal or hepatic insufficiency. It is also
contraindicated in patients who experienced metabolic and/or
vascular disorders during previous estrogen or progestogen
therapy, or who are allergic to the medication. The drug is
contraindicated in children.
• Side effects include vaginal spotting, and, in susceptible
individuals, signs of increased androgen activity such as acne, oily
skin, fluid retention, weight gain, hirsutism, voice change, or hair
loss.
• The drug has also been investigated for use as a
prospective contraceptive agent and as a postcoital contraceptive. It
also has been used to shrink uterine fibroids and to

15. STAY HEALTHY. THANK YOU