Estrogens and Androgens

Sex hormones produced by the gonads are necessary for : conception embryonic maturation development of primary and secondary sexual characteristics at puberty. All gonadal hormones are synthesized from cholesterol

The gonadal hormones are used in : replacement therapy. for contraception . management of menopausal symptoms. antagonists are effective in cancer chemotherapy

Estrogens Estradiol : is the most potent estrogen produced and secreted by the ovary. It is the principle estrogen in the premenopausal woman. Estrone : is a metabolite of estradiol. Estrone is the primary circulating estrogen after menopause. Estriol : metabolite of estradiol, It is present in significant amounts during pregnancy, because it is the principal estrogen produced by the placenta.

ethinyl estradiol : Synthetic estrogens, undergo less first-pass metabolism than naturally occurring steroids and, thus, are effective when administered orally at lower doses.

Therapeutic uses of estrogens contraception postmenopausal hormone therapy, also called estrogen- progestogen therapy (EPT). replacement therapy in premenopausal patients who are deficient in this hormone. Such a deficiency can be due to lack of development of the ovaries, premature menopause, or surgical menopause. `

Postmenopausal hormone therapy: The primary indication for estrogen therapy is menopausal symptoms such as vasomotor instability ( hot flashes) and vaginal atrophy. progestin is included with the estrogen therapy, because the combination reduces the risk of endometrial carcinoma associated with unopposed estrogen. Osteoporosis is effectively treated with estrogen.

Estrogen causes an increase in HDL and a decrease in LDL. bioavailability of estrogen taken orally is low due to first-pass metabolism in the liver. the drugs may be administered by transdermal patch, topical gel intravaginally, or by injection.

Adverse effects Nausea and breast tenderness. Postmenopausal uterine bleeding . estrogen therapy increase the risk of: thromboembolic events, myocardial infarction breast and endometrial cancer

Selective estrogen-receptor modulators (SERMs) SERM : Nonsteroidal compounds that bind to estrogen receptors and exert either estrogenic or antiestrogenic effects on target tissues. Tamoxifen raloxifene. Clomiphene .

Tamoxifen Considered to be the first SERM Theraputic uses: palliative treatment of metastatic breast cancer in postmenopausal women. It competes with estrogen for binding to the estrogen receptor in breast tissue.

Clomiphene It increases the secretion of gonadotropin-releasing hormone and gonadotropins, leading to a stimulation of ovulation. The drug has been used successfully to treat infertility associated with anovulatory cycles,

Progesterone, it is the natural progestin produced in response to luteinizing hormone (LH) by both females and by males . It is also synthesized by the adrenal cortex in both sexes. In females Progesterone promotes the development of a secretory endometrium that can accommodate implantation of a newly forming embryo.

The high levels of progesterone inhibit the production of gonadotropin and, therefore, prevent further ovulation. If conception takes place, progesterone continues to be secreted, maintaining the endometrium in a favorable state for the continuation of the pregnancy and reducing uterine contractions. If conception does not take place, the release of progesterone ceases abruptly. This decline stimulates the onset of menstruation.

Therapeutic uses of progestins hormonal deficiency for contraception, in which they are generally used with estrogens, either in combination or in a sequential manner. control of dysfunctional uterine bleeding, . treatment of dysmenorrhea. management of endometriosis.

synthetic progestins Norgestrel Levonorgestrel Medroxyprogesterone acetate is an injectable contraceptive. it is injected IM and has a duration of action of 3 months. Their clinical use mostly as oral contraceptives .

Anti progestins Mifepristone Administration of this drug to females early in pregnancy results, in most cases (up to 94 percent), in abortion of the fetus due to the interference with progesterone administration of misoprostol orally or intravaginally after a single oral dose of mifepristone effectively terminates gestation Uses: medical termination of pregnancy

Contraceptives Drugs that interfere with ovulation for prevention of pregnancy Major classes of contraceptives: Combination oral contraceptives. Progestin-only pills. Progestin implants.

Combination oral contraceptives Products containing a combination of an estrogen and a progestin are the most common type of oral contraceptives. Monophasic combination pills : contain a constant dose of estrogen and progestin given over 21 days. Triphasic oral contraceptive : contain a constant dose of estrogen with increasing doses of progestin given over three successive 7-day periods. With both type: active pills are taken for 21 days followed by 7 days of placebo.

It is taken for 21 consecutive days out of 28 It is taken for 21 consecutive days out of 28. start from the first day of the menstrual cycle to day 21,followed by 7pill- free days which causes withdrawal bleeding. Withdrawal bleeding occurs during the hormone-free interval Estrogens : ethinyl estradiol and mestranol. Progestins :norethindrone acetate, norgestrel,drospirenone.

the progestin- only pill ( mini pill) They are taken continuously (every day each time) They are less effective than combined pills. Irregular bleeding is common. used for patients who are breast-feeding ,are intolerant to estrogen, or are smokers. Injectable contraceptives: Medroxyprogesterone acetate injected/I.M./ 3months

Progestin implants One 4-cm capsule is placed SC in the upper arm and provides contraception for approximately 3 years. The effect is totally reversible when surgically removed. this method of contraception does not rely on patient compliance. side effects : irregular menstrual bleeding headaches

Mechanism of action It inhibits ovulation. The estrogen provides a negative feedback on the release of LH and FSH by the pituitary gland, thus preventing ovulation. The progestin also inhibits LH release and thickens the cervical mucus, thus hampering the transport of sperm. Withdrawal of the progestin stimulates menstrual bleeding during the placebo week.

nausea, vomiting wt gain. SIDE EFFECT nausea, vomiting wt gain. CV complication: deep venous thrombosis, pulmonary embolism, hypertension, MI

CONTRAINDICATIONS History of DVT,PE. CVA. Cardiovascular disease Heavy smoker &age >35. Pregnancy. Breast/endometrial cancer. Abnormal liver function.

Androgens They have anabolic,masculinizing effects in both males and females. Testosterone ,the most important androgen in humans, is synthesized in the testes and, in smaller amounts, by cells in the ovary of the female and by the adrenal gland in both sexes. dihydrotestosterone (DHT): androgens secreted by the testes testosterone secretion is controlled by GRH from the hypothalamus, which stimulates the anterior pituitary gland to secrete FSH ,LH.

androgens are required for : normal maturation in the male, sperm production, increased synthesis of muscle proteins and hemoglobin, decreased bone resorption.

Testosterone: It is ineffective orally because of inactivation by first-pass metabolism thus IM. Fluoxymesterone : given orally. Oxandrolone : orally active testosterone.

flutamide : act as competitive inhibitors of androgens at Anti androgens Finasteride: 5 -α reductase inhibitor Testosterone 5-α reductase Dihydrotestosterone (an active metabolite) (used for prostatic hyperplasia) flutamide : act as competitive inhibitors of androgens at used in the treatment of prostatic carcinoma.