Pharmacology of the Female Reproductive System

Pharmacology of the Female Reproductive System

• Hypothalamic-pituitary-ovarian Axis: This system regulates the female reproductive cycle. The hypothalamus releases GnRH, which stimulates the pituitary gland to release LH and FSH. These hormones act on the ovaries, stimulating the production of estrogens and progesterone, which are crucial for follicular growth and ovulation. The placenta also produces estrogens and progesterone during pregnancy.
• Hormonal Changes During the Menstrual Cycle: Hormonal levels fluctuate throughout the menstrual cycle. Estrogen levels rise during the follicular phase, peaking around ovulation, and then decline in the luteal phase. Progesterone levels increase during the luteal phase, preparing the uterus for pregnancy. LH and FSH levels also have characteristic patterns over the cycle.
• Actions of Progesterone: Progesterone is essential for the female reproductive system.
  • It promotes endometrial development during the luteal phase of the menstrual cycle.
  • It acts as a primary determinant for the onset of menstruation.
  • It stimulates mammary gland growth and development during pregnancy.
  • It thickens and reduces the amount of cervical mucus.
  • It increases basal body temperature.
  • It plays a vital role maintaining pregnancy.
• Actions of Estrogen (Estradiol):
  • Stimulates mammary gland growth during puberty.
  • Promotes endometrial proliferation during the follicular phase of the menstrual cycle.
  • Promotes proliferation of the vaginal epithelium.
  • Is weakly anabolic to bone.
  • Blocks resorption of bone.
  • Increases HDL and decreases LDL levels.
  • Is carcinogenic and thus increases the incidence of endometrial and breast cancer.
• General Pharmacological Properties of Estrogens and Progestins:
  • Progesterone and estradiol are rapidly inactivated when given orally.
  • Synthetic analogs are more useful in oral administration.
  • Various administration routes are often used.
• Some Synthetic Progestins: Different progestins are derived from testosterone and have androgenic activity. New generation progestins are designed to minimize adverse side effects like acne, hirsutism, nausea, and lipid changes. Some progestins have no pro-androgenic effect but instead have anti-androgenic activity.
• Some Synthetic Estrogens: Some examples include ethinyl estradiol, mestranol, and estrone sulfate.
• Hormonal Contraception in Females (Progestins Only):
  • Oral contraception types: Minipill (norethindrone, norgestrel)
  • Transdermal contraception
  • Vaginal rings (norethindrone, norgestrel)
  • IM injections: Depo-Provera (medroxyprogesterone acetate)
• Contraception: Progestins Only:
  • Effectiveness: 96-98%.
  • Mechanism of action: Prevents ovulation by inhibiting the hypothalamus and pituitary, decreases cervical mucus, alters endometrial receptiveness.
  • Adverse effects: Abnormal menstrual bleeding.
• Hormonal Contraception in Females (progestins + estrogens):
  • Oral: Norethindrone + ethinyl estradiol (21 on, 7 off)
  • Monophasic, biphasic and triphasic preparations
  • Other forms: IM injections, transdermal patches, vaginal rings.
  • Effectiveness: 97-98% but requires high patient compliance.
  • Mechanism of action: Prevents ovulation, changes cervical mucus viscosity, affects endometrial receptiveness.
  • Adverse effects: nausea, headaches, acne, hirsutism, cardiovascular effects in smokers >35, and metabolic/endocrine effects.
• Health Benefits of Progestins + Estrogens: Lower incidence of ovarian cysts, benign fibrocystic breast disease, endometrial/ovarian cancer, and increased HDL and decreased LDL levels.
• Examples of Combined Oral Contraceptives: Presents examples of varying estrogen and progestin doses for different body weights.
• Postcoital Contraceptives:
  • Types: estrogen alone, estrogen + progestin or progestin alone. High doses needed.
  • Effectiveness: 90-98%.
  • Mechanism of action: Prevents implantation in cases where fertilization has occurred.
  • Adverse effects: nausea, vomiting, headaches, dizziness, breast tenderness, and abdominal/leg cramps.
• Progesterone Receptor Antagonists:
  • Ulipristal: selective progesterone receptor modulator for emergency contraception.
  • Mifepristone (RU486): used for abortions (with a prostaglandin agonist) and postcoital contraception.
• Mifepristone (RU486), Abortion Pill:
  • Approved regimen used for terminating pregnancies up to 49 days from the LMP (2000 FDA approval).
  • A combination regimen of oral mifepristone followed by oral misoprostol within 48 hours.
• Contraceptive Methods Comparison: Provides data on contraceptive method use and relative failure rates in the US (Figure 25.7 and 25.8).
• Hormone levels of women and method of use related to 2016 statistics (page 25): Presents 2016 statistical data about contraceptive use among Palestinian women, highlighting methods of use and relative usage levels of different contraception types..
• Menopause: Estrogen decline results in many hormonal changes, affecting bone, vaginal, urination and mood changes, along with osteoporosis risk.
• Selective Estrogen Receptor Modulators (SERMs) and Estrogen Receptor Antagonists: Discusses the use of drugs like estradiol, clomiphene, tamoxifen, and raloxifene in different conditions, including breast cancer treatment, osteoporosis risk reduction, and ovulation induction.
  • Effects on bone, breast, cardiovascular system and uterus, are discussed.
• Use of SERMs: Relief of post-menopausal symptoms, osteoporosis treatment. The less risk of side effects associated with estrogen treatments including vaginal bleeding, breast swelling, and increased risk of endometrial and breast cancer related to estrogen treatment.
• Other SERMs like tamoxifen and use: Treatment of breast cancer, but increased risk of endometrial cancer and thromboembolic disease, Induction of ovulation and reduced return of cancer, are noted.
• Aromatase Inhibitors:
  • Inhibits the conversion of testosterone to estradiol, useful in breast cancer treatment.
  • Different types are cited (steroidal and non-steroidal, like Formestane, Exemestane, Anastrozole, and Letrozole).
• Fertility Drugs:
  • Clomiphene citrate: blocks estrogen receptors, but response may be ineffective for women with PCOS.
  • Gonadotropins: effective in inducing ovulation but more expensive and need injectable route with increased risk for multiple pregnancies.
  • Letrozole: also used in women with breast cancer. Aromatase inhibition leads to suppression of estrogen production with pituitary producing more hormones to stimulate ovaries. Can cause ovulation in women.
• Letrozole vs. Clomiphene: Research comparing their effectiveness in treating PCOS, noting ovulation rates, live birth rates, and benefits for obese women. No difference in risk of pregnancy loss or multiple pregnancies.
• Pharmacology Of Gonadotropins: Discusses use of these hormones as diagnostic tools (LH for ovulation, CG for pregnancy) and as therapeutic agents (FSH or FSH + LH to induce follicular growth or induce ovulation, CG for cryptorchidism, FSH, LH, or CG for hypogonadotropic hypogonadism).
• Cabergoline (Dostinex): Dopamine receptor agonist for hyperprolactinemia (idiopathic or pituitary adenomas). Long half-life (approximately 80 hours) with twice-weekly dosing commonly used.
• Bromocriptine: Similar use as Cabergoline but given twice daily.
• Endometriosis: Explains what endometriosis is, its common causes and symptoms. Discusses treatment options, including surgery, NSAIDS, hormonal contraceptives like continuous-cycle regimens and Gonadotropin-releasing hormone (Gn-RH) agonists/antagonists. Discuss how GnR agonists/antagonists can decrease ovarian hormone production and shrink endometrial tissue. Reviews aromatase inhibitors as treatment.
• Pharmacology of the Male Reproductive System: Briefly introduces the hypothalamic-pituitary-testicular axis and androgen biosynthesis.
• Androgen Biosynthesis: Details the steps in creating testosterone, highlighting the initial production of cholesterol through various steps.
• Actions of Androgens: Describes the effects of these hormones on virilization, puberty, maintaining secondary sexual characteristics, supporting spermatogenesis, and promoting anabolic reactions.
• Testosterone Preparations: Presents different testosterone preparations for replacement therapy, noting various routes (IM, SC, O, S.L.), as well as other related hormones.
• Testosterone for Anabolism: Describes specific androgens like Ethylestrenol, Stanozolol, Oxandrolone, Nandrolone decanoate, and Methandienone use in anabolic states like osteoporosis and muscular growth.
• Androgen Therapy: Discusses the uses of androgen therapy, including replacement therapy in cases of male hypogonadism, treating catabolic states like osteoporosis or recovery from surgery, and growth treatment combined with other hormones.
• 5 alpha-reductase Inhibitors: Specifically finasteride, explains how it helps treat Benign Prostatic Hyperplasia.
• Anti-androgens:
  • Describes certain types, useful in cases of prostate cancer, hirsutism, and congenital adrenal hyperplasia (CAH), along with discussing male precocious puberty.
  • Reviews androgen deprivation therapy (ADT) for metastatic castrate-resistant prostate cancer (CRPC), highlighting luteinizing hormone-releasing hormone agonists (LH-RH Agonists) and its downsides when used as long-term therapy, such as loss of libido and insulin sensitivity issues.
  • Notes certain steroidal and non-steroidal examples (e.g. Cyproterone acetate, CPA).
• Nonsteroidal Antiandrogens: Discusses the first and second generations of these drugs with mechanisms and their FDA approval status, especially useful for men with metastatic CRPC.
• CYP17 Inhibitors: Explains that Ketoconazole is a competitive inhibitor of various cytochrome P450 enzymes, including CYP17. Abiraterone acetate acts on CYP17 and has fewer side effects than ketoconazole, and is initially presented when progression to CRPC is diagnosed.
• Pharmacology Of GnRH: Describes leuprolide, a GnRH agonist, and its use in simulating gonadotropin secretion and desensitizing the pituitary gland to suppress gonadotropin secretion to treat precocious puberty in boys and other male hormonal disorders.
• Important Note: The summary provides a general overview and does not include every detail that may have been discussed in all of the original slides.

Explore the intricate pharmacological aspects of the female reproductive system, including the hypothalamic-pituitary-ovarian axis and hormonal variations during the menstrual cycle. Understand the actions of key hormones like estrogens and progesterone in regulating reproductive functions. This quiz provides a comprehensive overview essential for pharmacy and medical students.