L16. Pharmacology - Reproductive Pharmacology
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Questions and Answers

What is the primary purpose of using lutropin α in women with anovulation?

  • To provide nutritional support during pregnancy
  • To enhance the effects of clomiphene
  • To stimulate follicle development after ovulation
  • To induce follicle development and trigger ovulation (correct)

Which of the following statements about the administration of hCG is correct?

  • It is only given orally due to patient preference.
  • It is administered daily through subcutaneous or intramuscular injections. (correct)
  • It is administered via subcutaneous or intravenous routes.
  • It can only be given once a week for effectiveness.

What are the typical signs of hypogonadism in males that may be treated with exogenous androgen?

  • Increased muscle mass and aggression
  • Reduced libido and infertility (correct)
  • Excessive hair growth and weight loss
  • Low body temperature and fatigue

What serious complication of treatment is most commonly associated with ovarian stimulation in women?

<p>Ovarian hyperstimulation syndrome (C)</p> Signup and view all the answers

Which of the following conditions is NOT typically treated with ovulation induction agents like lutropin α?

<p>Primary ovarian insufficiency (D)</p> Signup and view all the answers

What enzyme is responsible for cleaving the long side chain of cholesterol to form pregnenolone?

<p>CYP11A1 (A)</p> Signup and view all the answers

Which reaction is NOT catalyzed by CYP17A1?

<p>Aromatization (C)</p> Signup and view all the answers

What is the product formed from the metabolism of pregnenolone by CYP17A1?

<p>Dehydroepiandrosterone (DHEA) (C)</p> Signup and view all the answers

Which enzyme converts testosterone into dihydrotestosterone?

<p>5α-reductase (D)</p> Signup and view all the answers

Where are androgens primarily converted to estrogens?

<p>Ovary and adipose tissue (B)</p> Signup and view all the answers

Which statement about pregnenolone is correct?

<p>It can metabolize to adrenal androgens. (A)</p> Signup and view all the answers

What major steroid does progesterone convert into after further metabolism?

<p>Estradiol (B)</p> Signup and view all the answers

Which estrogen is considered the most potent naturally occurring estrogen?

<p>17β-estradiol (E2) (D)</p> Signup and view all the answers

Which enzyme is primarily responsible for the aromatization of precursor androgens to estrogens?

<p>CYP19 (D)</p> Signup and view all the answers

Which tissues exhibit high expression of CYP19 for estrogen production?

<p>Ovary and placenta (B)</p> Signup and view all the answers

After menopause, where does the majority of circulating estrogen in women originate from?

<p>Adipose tissue (C)</p> Signup and view all the answers

What are the two subtypes of nuclear estrogen receptors?

<p>ERα and ERβ (C)</p> Signup and view all the answers

Which of the following tissues is NOT capable of aromatizing androgens to estrogens?

<p>Cardiac tissue (C)</p> Signup and view all the answers

What mechanism do nuclear estrogen receptors operate through?

<p>Ligand-activated transcription factors (D)</p> Signup and view all the answers

Which term best describes the common activity shared by all estrogens?

<p>Feminizing activity (D)</p> Signup and view all the answers

In men, which tissue serves as the main source of circulating estrogens?

<p>Adipose tissue (C)</p> Signup and view all the answers

What is a significant factor in the growth of breast cancers?

<p>Expression of estrogen receptors (D)</p> Signup and view all the answers

Which condition is characterized by the growth of endometrial tissue outside the uterus?

<p>Endometriosis (B)</p> Signup and view all the answers

How does continuous administration of GnRH influence pituitary function?

<p>It suppresses pituitary gonadotroph activity (D)</p> Signup and view all the answers

What is required for the conversion of testosterone to DHT in prostate tissue?

<p>5α-reductase (B)</p> Signup and view all the answers

What initiates the release of gonadotropins from the pituitary gland?

<p>Pulsatile secretion of GnRH (B)</p> Signup and view all the answers

What is the role of GnRH in the reproductive hormone regulation?

<p>It promotes the production of LH and FSH (C)</p> Signup and view all the answers

What type of growth is associated with benign prostatic hyperplasia (BPH)?

<p>Androgen-dependent growth (C)</p> Signup and view all the answers

What effect does the administration of anti-estrogens have on breast cancer cells expressing ER?

<p>It inhibits growth (B)</p> Signup and view all the answers

Which hormone does GnRH primarily stimulate the secretion of from the pituitary?

<p>Follicle-stimulating hormone (FSH) (D)</p> Signup and view all the answers

Which of the following conditions is a contraindication for estrogen use?

<p>History of thromboembolic disorder (D)</p> Signup and view all the answers

What is a common adverse effect associated with progestin-only contraceptive drugs?

<p>Breakthrough bleeding (A)</p> Signup and view all the answers

What is the primary mechanism by which combination estrogen-progestin contraceptives inhibit ovulation?

<p>Inhibition of GnRH, LH, and FSH secretion (B)</p> Signup and view all the answers

Which of the following hormones is primarily used in combination contraceptives?

<p>Mestranol (D)</p> Signup and view all the answers

Which of the following is a potential outcome of unopposed estrogen use in women with a uterus?

<p>Risk of endometrial cancer (B)</p> Signup and view all the answers

Which progestin-related adverse effect is associated with androgen-like progestins?

<p>Hirsutism (D)</p> Signup and view all the answers

Which type of oral contraceptive is characterized by a constant dose of estrogen and progestin throughout the cycle?

<p>Monophasic (A)</p> Signup and view all the answers

What effect does combination contraceptives have on cervical mucus?

<p>Decreases viscosity, hindering sperm movement (D)</p> Signup and view all the answers

What is the primary purpose of administering progestin alongside estrogen in contraceptive therapies?

<p>To limit uterine growth (A)</p> Signup and view all the answers

Which of the following describes the incidence of venous thromboembolic disease in users of combination oral contraceptives?

<p>Approximately 3-fold higher than non-users (C)</p> Signup and view all the answers

Flashcards

CYP11A1 (P450scc)

An enzyme that catalyzes the cleavage of the side chain of cholesterol, forming pregnenolone.

Progesterone

The major endogenous progestin, produced in the ovaries, placenta, and adrenal gland.

CYP17A1

An enzyme that catalyzes both 17-hydroxylation and side chain cleavage of pregnenolone and 17-hydroxypregnenolone.

Dehydroepiandrosterone (DHEA)

The product of 17-hydroxylation and side chain cleavage of pregnenolone by CYP17A1.

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Adrenal Androgens

Androgens produced in the adrenal gland and testes.

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Testosterone

The main type of male sex hormone, produced in the testes.

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5α-reductase

An enzyme that converts testosterone to dihydrotestosterone, important for androgen target cells.

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Estrogens

A group of hormones that share a common feminizing effect in the body.

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17β-estradiol (E2)

The most potent naturally occurring estrogen.

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Estrone (E1) and Estriol (E3)

Estrogens that are less potent than 17β-estradiol.

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Aromatization

The process of converting androgens into estrogens.

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CYP19 (aromatase)

The enzyme responsible for catalyzing the aromatization process.

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Ovary and placenta

The primary sites of estrogen production through aromatization.

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Adipose tissue, hypothalamic neurons, muscle

Other tissues capable of aromatizing androgens into estrogens.

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Adipose tissue

The primary source of estrogens in postmenopausal women.

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Nuclear estrogen receptors (ERα and ERβ)

The mechanism by which estrogens exert their effects in the body.

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Estrogen-progestin combination contraceptive

A type of contraceptive containing both estrogen and progestin to prevent pregnancy. They work by suppressing ovulation. It is important to know this to effectively advise patients on different contraceptive options.

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Monophasic contraceptive

An oral contraceptive that delivers a constant dose of estrogen and progestin throughout the menstrual cycle.

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Multiphasic contraceptive

An oral contraceptive where the dosage of estrogen and/or progestin changes during the menstrual cycle, aiming to better mimic natural hormonal fluctuations.

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Progestin-only contraceptive

Oral contraceptives containing only progestin.

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Ethinyl estradiol

A common estrogen used in combination oral contraceptives. It is a synthetic form of estrogen.

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Mestranol

A common estrogen used in combination oral contraceptives. It is a less potent form of estrogen.

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Breakthrough bleeding

A potential adverse effect of oral contraceptives, characterized by bleeding during the usual time of menstruation, even when taking the contraceptive.

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Weight gain

A potential adverse effect of oral contraceptives, where there is an increase in body weight.

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Increased skin pigmentation

A potential adverse effect of oral contraceptives, where there is an increase in the number and size of dark spots on the skin.

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Endometrial hyperplasia

A condition leading to inflammation and thickening of the uterus's lining, potentially increasing the risk of uterine cancer.

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Endometriosis

A condition where endometrial tissue grows outside the uterus, often causing pelvic pain and infertility.

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Breast Cancer

A type of cancer that originates in the breast tissue.

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Benign Prostatic Hypertrophy (BPH)

An enlargement of the prostate gland, typically associated with aging.

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Prostate Cancer

A type of cancer that affects the prostate gland.

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Gonadotropin-Releasing Hormone (GnRH)

A hormone produced in the hypothalamus that stimulates the release of other hormones from the pituitary gland, specifically LH and FSH.

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GnRH Agonist

A type of drug that mimics the action of GnRH, leading to a surge in hormone release followed by suppression.

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GnRH Antagonist

A type of drug that blocks the action of GnRH, preventing the release of other hormones.

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Continuous GnRH Administration

The process of continuously stimulating the GnRH receptor with an agonist, leading to suppression of hormone release.

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GnRH

The hormone that regulates the release of gonadotropins from the pituitary gland.

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Pituitary Gland

The pituitary gland, located at the base of the brain, controls the release of many hormones, including gonadotropins.

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Lutropin α (LH)

A hormone used to induce ovulation in women with anovulation. It's a recombinant form of human LH, but was withdrawn in 2016 due to safety concerns.

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Chorionic Gonadotropin (hCG)

A hormone extracted from urine or made recombinantly. It's used for different purposes, including inducing ovulation in women and treating male infertility.

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Ovarian Hyperstimulation Syndrome (OHSS)

A serious condition that can occur in women undergoing ovulation induction with hormones like hCG or LH. It involves overstimulation of the ovaries, leading to fluid buildup in the abdominal cavity.

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Hypogonadism

A condition resulting from inadequate production of hormones by the testicles, affecting male fertility and other functions.

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LH and FSH for Male Infertility

Treatment for infertility in hypogonadal men often involves using both LH and FSH (follicle-stimulating hormone) to promote sperm production. These hormones work in a coordinated way.

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Study Notes

Reproductive Pharmacology Lecture Notes

  • This lecture covers pharmacological agents used in reproductive pharmacology, including endogenous molecules (e.g., steroid hormones, peptide hormones) and synthetic drugs.

Session Learning Objectives

  • Identify classes of gonadal steroids and describe their effects and mechanisms.
  • Detail clinical uses of gonadal steroids, considering administration routes, combinations, adverse effects, and contraindications.
  • Describe classes of drugs used to modify gonadal steroid actions.
  • Explain the clinical use of oxytocin.

Session Outline

I. Overview of Pharmacological Classes

  • The lecture covers classes of pharmacological agents for reproductive processes.
  • Includes endogenous and synthetic molecules.

II. Gonadal Steroids

  • Brief review and introduction to compounds.
    • Estrogens
    • Progestins
    • Androgens
  • Steroid hormone biosynthesis begins with cholesterol.
  • CYP11A1 (aka P450scc) cleaves the long side chain of cholesterol to form pregnenolone.
  • Pregnenolone can be converted directly to progesterone (major progestin).
  • Pregnenolone is metabolized by CYP17A1 to produce DHEA and androstenedione (adrenal androgens).
  • Androgens are converted to testosterone.
  • Testosterone can be converted into dihydrotestosterone (DHT).
  • Androgens are converted to estrogens by aromatization (CYP19).

III. Clinical Uses of Gonadal Steroids

  • Female hormone replacement therapy
    • Primary hypogonadism
    • Postmenopausal hormonal therapy
  • Contraception
    • Combination estrogen-progestin contraceptives
    • Progestin-only contraception
    • Emergency contraception
  • Use of androgens and anabolic steroids
    • Replacement therapy in hypogonadism
    • Other reported uses
    • Adverse effects and contraindications

IV. Modulators of Gonadal Steroid Action

  • Gonadotropin releasing hormone (GnRH) agonists
  • GnRH receptor antagonists
  • Gonadotropins
  • Aromatase inhibitors
  • Selective estrogen receptor modulators (SERMs)
  • 5α-reductase inhibitors
  • Androgen receptor antagonists
  • Progesterone receptor antagonists

V. Oxytocin

  • Uses
  • Adverse effects and contraindications

I. Overview of Pharmacological Classes

  • Covers pharmacological agents used in reproductive processes, including endogenous molecules (like steroid hormones) and synthetic drugs.

A. Estrogens

  • 17β-estradiol (E2) is the most potent naturally occurring estrogen.
  • Estrone (E1) and estriol (E3) are less potent.
  • All estrogens are derived from aromatization of androgens.
  • Ovaries and placenta have high CYP19 (aromatase) expression.
  • Certain non-reproductive tissues can aromatize androgens.
  • After menopause, adipose tissue is a major source of estrogen.

B. Progestins

  • Natural progestin is progesterone.
  • Required for pregnancy maintenance.
  • Synthetic derivatives have varying effects (estrogenic, anti-estrogenic, etc.).
  • Many have other hormonal effects (e.g., estrogenic, anti-estrogenic, androgenic, etc.).
  • Some are chemically and pharmacologically similar to progesterone (e.g., hydroxyprogesterone, medroxyprogesterone, etc.).
  • Some are 17-ethinyl testosterone derivatives (e.g., dimethisterone) or 19-nortestosterone derivatives (e.g., norethindrone).
  • Some third-generation compounds (e.g., desogestrel) have lower androgenic activity.

C. Androgens

  • Essential for male sexual development and maturation, and sex characteristics.
  • DHEA and androstenedione are adrenal androgens.
  • Testosterone is the main circulating androgen.
  • DHT is the most potent intracellular androgen.
  • Testosterone is a prohormone.
  • 5α-reductase converts testosterone into DHT.

III. Clinical Uses of Gonadal Steroids

  • Female Hormone Replacement Therapy: Primary hypogonadism, Postmenopausal hormonal therapy
  • Contraception: Combination estrogen-progestin, Progestin-only, Emergency
  • Androgens and Anabolic Steroids: Replacement therapy, other uses, adverse effects, contraindications.

IV. Modulators of Gonadal Steroid Action

  • Drugs that modify the action of gonadal steroids
  • Includes agonists, antagonists and other related agents.

V. Oxytocin

  • A 9 amino acid peptide hormone.
  • Secreted by the posterior pituitary.
  • Stimulates uterine contractions (labor).
  • Involved in milk ejection.
  • Clinical uses include inducing labor, etc.
  • Short half-life.

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Description

Explore the pharmacological agents involved in reproductive health, focusing on both endogenous molecules and synthetic drugs. Learn about gonadal steroids, their clinical uses, and the mechanisms underlying their actions, including the role of oxytocin. This lecture provides a comprehensive review for understanding reproductive pharmacology.

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