Sex hormones - Progestogens

Sex hormones Dr. Entisar Al-Mukhtar
Progestogens
Progesterone, is the natural progestogen, produced in response to LH by both females (secreted by corpus luteum & placenta) & males (secreted by the testes). It is also synthesized by the adrenal cortex in both sexes.

Mechanism of action
• In females, progesterone promotes the development of a secretory endometrium.
• High levels of progesterone released during luteal phase of the menstrual cycle inhibit the production of gonadotropin & therefore, prevent further ovulation.
• If conception does not take place, the release of progesterone from the corpus luteum ceases abruptly. This decline stimulates the onset of menstruation.



PROGESTOGENS
Desogestrel USED IN MANY COMBINATIONS
Dienogest (w/estradiol valerate)
NATAZIA
Drospirenone (w/ethinyl estradiol)
BEYAZ, YAZ, YASMIN
Etonogestrel (w/ethinyl estradiol)
NUVA RING
Etonogestrel (subdermal)
IMPLANON, NEXPLANON
Levonorgestrel MIRENA, NEXT CHOICE,
PLAN B ONE-STEP
Medroxyprogesterone PROVERA
Norelgestromin (w/ethinyl estradiol)
ORTHO EVRA
Norethindrone NOR-QD, ORTHO MICRONOR
Norethindrone acetate AYGESTIN
Norgestimate USED IN MANY COMBINATIONS
Norgestrel (w/ethinyl estradiol) LO/
OVRAL
Progesterone USED IN MANY COMBINATIONS

PROGESTERONE AGONIST/ANTAGONIST
Ulipristal acetate ELLA

PROGESTERONE ANTAGONIST
Mifepristone MIFEPREX

Therapeutic uses of progestogens
1. Hormonal deficiency.
2. Contraception: progestogens are generally used with estrogens, either in combination or in a sequential manner.
• Progesterone by itself is not used widely as a contraceptive therapy because of its rapid metabolism.
• Synthetic progestogens (progestins) used in contraception are more stable to first-pass metabolism, they include Desogestrel, Dienogest, Drospirenone, Levonorgestrel, Norethindrone, Norethindrone acetate, Norgestimate, & Norgestrel.
• Medroxyprogesterone acetate is used as injectable contraceptive while its oral form is used in postmenopausal HT.
• Progestins are also used for the control of dysfunctional uterine bleeding, dysmenorrhea & management of endometriosis & infertility.

Pharmacokinetics
• The micronized preparation of progesterone is rapidly absorbed after oral administration & has a short half-life in the plasma.
• Synthetic progestins are less rapidly metabolized.
• Oral medroxyprogesterone acetate has a half-life of 30 days, when injected IM or SC it has a half-life of about 40-50 days & provides contraception for approximately 3 months.
• The half-lives of other progestins are 1-3 days, allowing for once-daily dosing.

Adverse effects
• Headache, depression, weight gain & changes in libido.
• The 19-nortestosterone derivatives (e.g, norethindrone, norethindrone acetate, norgestrel, levonorgestrel), possess some androgenic activity & can cause acne & hirsutism. Less androgenic progestins, such as norgestimate & drospirenone, may be preferred in women e.g., with acne.
• Drospirenone has antimineralocorticoid effects, and its concurrent use with other drugs that increase serum potassium (e.g., ACEIs) may increase the risk of hyperkalemia.

Antiprogestin
Mifepristone
• A progesterone antagonist with partial agonist activity (note: mifepristone also has potent antiglucocorticoid activity), its administration in early pregnancy usually results in abortion due to interference with the progesterone.
• Mifepristone is often combined with the PGE1 analog misoprostol (orally or I.V) to induce uterine contractions.
• The major adverse effects are uterine bleeding & possibly an incomplete abortion.
• Mifepristone has also been investigated as an oral & an emergency contraceptive.