EHADA EMMANUEL 17/MHS03/013 (A) ESTROGEN Estrogen, or oestrogen, is the primary female sex hormone. it is responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens in females that have estrogenic hormonal activity: estrone, estradiol, and estriol. The estrane steroid estradiol is the most potent and prevalent of these. TYPES and EXAMPLE The four major naturally occurring estrogens in women are estrone (E1), estradiol (E2), estriol (E3), and estetrol (E4). Estradiol is the predominant estrogen during reproductive years both in terms of absolute serum levels as well as in terms of estrogenic activity. During menopause, estrone is the predominant circulating estrogen and during pregnancy estriol is the predominant circulating estrogen in terms of serum levels. Given by subcutaneous injection in mice, estradiol is about 10-fold more potent than estrone and about 100-fold more potent than estriol.[10] Thus, estradiol is the most important estrogen in non-pregnant females who are between the menarche and menopause stages of life. However, during pregnancy this role shifts to estriol, and in postmenopausal women estrone becomes the primary form of estrogen in the body. Another type of estrogen called estetrol (E4) is produced only during pregnancy. All of the different forms of estrogen are synthesized from androgens, specifically testosterone and androstenedione, by the enzyme aromatase. BIOLOGICAL FUNCTION The actions of estrogen are mediated by the estrogen receptor (ER), a dimeric nuclear protein that binds to DNA and controls gene expression. Like other steroid hormones, estrogen enters passively into the cell where it binds to and activates the estrogen receptor. The estrogen:ER complex binds to specific DNA sequences called a hormone response element to activate the transcription of target genes (in a study using an estrogen-dependent breast cancer cell line as model, 89 such genes were identified). Since estrogen enters all cells, its actions are dependent on the presence of the ER in the cell. The ER is expressed in specific tissues including the ovary, uterus and breast. The metabolic effects of estrogen in postmenopausal women has been linked to the genetic polymorphism of the ER. While estrogens are present in both men and women, they are usually present at significantly higher levels in women of reproductive age. They promote the development of female secondary sexual characteristics, such as breasts, and are also involved in the thickening of the endometrium and other aspects of regulating the menstrual cycle. In males, estrogen regulates certain functions of the reproductive system important to the maturation of sperm and may be necessary for a healthy libido. MEDICAL USE Estrogens are used as medications, mainly in hormonal contraception, hormone replacement therapy, and to treat gender dysphoria in transgender women and other transfeminine individuals as part of feminizing hormone therapy. (B) PROGESTINS progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a synthetic progestogen. Progestogens are used most commonly in hormonal birth control and menopausal hormone therapy. They can also be used in the treatment of gynecological conditions, to support fertility and pregnancy, to lower sex hormone levels for various purposes, and for other indications. Progestogens are used alone or in combination with estrogens. They are available in a wide variety of formulations and for use by many different routes of administration.[Examples of progestogens include natural or bioidentical progesterone as well as progestins such as medroxyprogesterone acetate and norethisterone. MEDICAL USES BIRTH CONTROL: Progestogens are used in a variety of different forms of hormonal birth control for women, including combined estrogen and progestogen forms like combined oral contraceptive pills, combined contraceptive patches, combined contraceptive vaginal rings, and combined injectable contraceptives; and progestogen-only forms like progestogen-only contraceptive pills ("mini-pills"), progestogen-only emergency contraceptive pills ("day-after pills"), progestogen-only contraceptive implants, progestogen-only intrauterine devices, progestogen-only contraceptive vaginal rings, and progestogen-only injectable contraceptives. MENSTRUAL DISORDERS: Progestogens are used to treat menstrual disorders such as secondary amenorrhea and dysfunctional uterine bleeding. In a normal menstrual cycle, declining levels of progesterone trigger menstruation. Progestogens such as norethisterone acetate and medroxyprogesterone acetate may be used to artificially induce progesterone-associated breakthrough bleeding. The progestogen challenge test or progestogen withdrawal test is used to diagnose amenorrhea. Due to the availability of assays to measure estrogen levels, it is now rarely used. SIDE EFFECTS Progestogens have relatively few side effects at typical dosages. Side effects of progestogens may include tiredness, dysphoria, depression, mood changes, menstrual irregularities, hypomenorrhea, edema, vaginal dryness, vaginal atrophy, headaches, nausea, breast tenderness, decreased libido. Progestins with androgenic activity, namely 19-nortestosterone derivatives, can also cause acne, hirsutism, seborrhea, voice deepening, changes in liver protein production (e.g., decreased HDL cholesterol, sex hormone-binding globulin), increased appetite, and weight gain, among others. Other side effects of progestogens may include an increased risk of breast cancer, cardiovascular disease, and blood clots, among others. Some of the side effects of progestogens are due not to their progestogenic activity but rather due to off-target activities (e.g., androgenic activity, glucocorticoid activity, antimineralocorticoid activity). At high doses, due to their antigonadotropic effects, progestogens can cause low sex hormone levels and associated side effects like diminished secondary sexual characteristics, sexual dysfunction (e.g., reduced sex drive and erectile dysfunction), reversible infertility, reduced bone mineral density, and an increased risk of bone fractures, both in men and in premenopausal women. Question 2: Drugs used as anti-fertility drugs Anti fertility drugs are drugs that control fertility. They are also called oral contraceptives. These drug affect and are involved in the menstrual cycle and ovulation in females . Estrogen and progestene in the combined form are given as birth control pills. The anti fertility substance is active in females when it: (I) prevents ovulation (II) prevents implantation (III) prevents fertilization In males when it: (I) inhibits testosterone (II) prevents spermatogenesis (III) causes mortality of sperm EXAMPLES OF SUCH DRUGS INCLUDE: (I) Dinestrol (II) Norgestrel (III) Norethynodrel (IV) Norethindrone (V) Mestranol