Estrogen and Ovarian Cycle Overview
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Questions and Answers

What are the three main types of natural estrogens?

  • Estradiol, Estrone, Estriol
  • Estradiol, Estrogen, Estriol
  • Estrogen, Estrogen, Estrone
  • Estradiol, Estriol, Estrone (correct)

    • Which of the following is the major estrogen secreted by ovaries?

  • Estradiol (correct)
  • Estrone
  • Estriol
  • All of the above

    • Estrone is a major estrogen produced by the adrenal glands during post menopause.

    True

    Which of these is associated with an increased risk of breast cancer in both sexes?

    <p>Phenols</p> Signup and view all the answers

    What is the primary function of Clomiphene (Clomid)?

    <p>To induce ovulation</p> Signup and view all the answers

    Which of the following is a synthetic estrogen?

    <p>Ethinyl estradiol</p> Signup and view all the answers

    What is the primary function of Danazol (Danocrine)?

    <p>To suppress ovarian function</p> Signup and view all the answers

    What is the primary function of Tamoxifen (Nolvadex)?

    <p>To treat breast cancer</p> Signup and view all the answers

    Which medication is approved for the prevention of postmenopausal osteoporosis?

    <p>Raloxifene</p> Signup and view all the answers

    What is the primary function of Fulvestrant (Faslodex)?

    <p>To treat breast cancer</p> Signup and view all the answers

    What is the name of the receptor that estrogens bind to?

    <p>Estrogen Receptor (ER)</p> Signup and view all the answers

    There are two subtypes of estrogen receptors: ER alpha and ER beta.

    <p>True</p> Signup and view all the answers

    Estrogen receptors are primarily found in the cell cytoplasm.

    <p>False</p> Signup and view all the answers

    What is the name of the process where estrogen induces the formation of proteins involved in cellular processes?

    <p>Transcriptional Activation</p> Signup and view all the answers

    What is the primary mechanism of action of Anastrozole (Arimidex)?

    <p>It inhibits aromatase enzyme</p> Signup and view all the answers

    What is the primary mechanism of action of Clomiphene (Clomid)?

    <p>Increases LH and FSH levels</p> Signup and view all the answers

    What is the primary function of estrogen inhibitors?

    <p>To prevent the development of breast cancer</p> Signup and view all the answers

    Estrogen's use is limited to treating female reproductive issues.

    <p>False</p> Signup and view all the answers

    Estrogens are contraindicated in women with a history of thromboembolic disorders.

    <p>True</p> Signup and view all the answers

    What is the name of the condition characterized by cysts on the ovaries, excessive androgen production, and irregular menstrual cycles?

    <p>Polycystic Ovary Syndrome (PCOS)</p> Signup and view all the answers

    Patients with PCOS are at an increased risk of developing endometrial cancer.

    <p>False</p> Signup and view all the answers

    Which of the following conditions is commonly treated with Danazol (Danocrine)?

    <p>Endometriosis</p> Signup and view all the answers

    Anastrozole (Arimidex) is primarily used to treat breast cancer.

    <p>True</p> Signup and view all the answers

    Study Notes

    Estrogens

    • Natural human estrogens
    • Phytoestrogens (Soy, saw palmetto)
    • Estrogens in ocean sediments
    • Phenols
    • Used in plastic manufacturing
    • Associated with increased breast cancer risk in both sexes

    Ovarian Cycle

    • Granulosa cells essential for stages of ovarian cycle
    • Theca folliculi cells are also involved in production. (Stage 2)
    • Primary oocyte in zona pellucida (Stage 3)
    • Secondary oocyte and Corona radiata ( Stage 4 )
    • Ovarian and Endometrial cycles
    • Estrogen and progesterone levels fluctuate throughout the cycle. Graph shows hormone levels during cycles with and without conception.
    • Various stages of follicular and luteal phases are shown with hormone measurements.
    • Various stages detailed with a diagram relating to stages.

    Natural Estrogens

    • Estradiol (E2), Estrone (E1), Estriol (E3)
    • E2 is the primary estrogen secreted by the ovaries
    • E1 and E3 are primarily produced through liver conversion or from adrenal androgens
    • Estrogen production occurs in ovarian follicles by theca and granulosa cells (pre-ovulation)
    • Post-ovulation, estrogen is produced by theca and granulosa cells of the corpus luteum
    • Progesterone also produced during ovulation
    • Pregnancy involves estrogen production from the placenta and fetus
    • Estrogen levels fluctuate monthly with the ovarian cycle (lowest in early follicular, highest right before ovulation)
    • E2 has higher affinity for estrogen receptor compared to E1 and E3.

    Estrogen Production

    • Estrogen production involves the cooperation of theca and granulosa cells under regulatory LH (luteinizing hormone) and FSH (follicle-stimulating hormone)
    • Cholesterol is the precursor to estrogen production in theca cells.
    • Enzymes like 3β-HSD, 17α-hydroxylase, 17,20 lyase, and 17β-HSD play roles in converting cholesterol to pregnenolone then progesterone, Androstenedione and Testosterone.
    • Aromatase enzyme in granulosa cells converts androgens to estrogens.

    Estrogen Source

    • Ovaries are the primary source of estrogen in premenopausal women
    • Estrogen is primarily produced by adrenal glands in post-menopausal women (estrone).
    • Also produced by ovarian follicles, corpus luteum and placenta with lesser amounts produced by liver, breast tissue and adrenal glands.

    Pharmacokinetics

    • Estrogens bind to SHBG (sex hormone-binding globulin) in the blood with high affinity and albumin with lower affinity
    • Estrogen is converted to estrone and estriol in the liver and other tissues.
    • Some estrogen derivatives (Estrone and Estriol) are secreted into bile.
    • Oral estrogens have a higher ratio of liver to peripheral effects compared to Transdermal and Cream forms.
    • Increased clotting factors and renin levels may occur with estrogen therapies.
    • Estrogens are excreted into breast milk.

    Synthetic Estrogens

    • Chemical alterations are used to enhance oral efficacy
    • Types of synthetic estrogens: steroidal and non-steroidal
    • Some are prodrugs such as Quinestrol which produces Ethinyl estradiol
    • Conjugated equine estrogens (Premarin, Enjuvia, Cenastin) are used
    • Esterified forms of synthetic estrogens
    • Non-steroidal Forms (diethylstilbestrol (Stilbestrol), dienestrol, benzestrol, hexestrol, chlorotrianisene
    • Specific uses may differ for prostate cancer today.

    Mechanism of Action

    • Bound to SHBG in plasma, then dissociates to enter cells
    • Travels to the nucleus and binds to estrogen receptor (ER)
    • Estrogen binding causes dissociation of ER from HSP90
    • ER and receptor-ligand complex dimerizes and binds estrogen response elements (EREs) on DNA
    • Transactivation complex forms by recruitment of co-regulators and transcription factors (TFs).
    • Two ER subtypes: alpha and beta
    • Alpha has effects on uterus, breast tissue, bone maintenance, etc
    • Beta has immune and nervous system effects.
    • Estrogens have non-genomic effects and are responsible for rapid responses.

    Physiological Effects

    • Sexual maturation: estrogen stimulates growth and development, promotes development of genitalia (vagina, uterus, Fallopian tubes).
    • Breast, uterine, and secondary sex characteristic development
    • Endometrial effects: endometrial lining development is dependent on estrogen
    • Metabolic and Cardiovascular: estrogen influences bone health, adiposity, circulating levels of lipids and blood clotting factors.

    Uses

    • Primary hypogonadism: estrogen therapy mimics puberty development
    • Post-menopausal HRT: addresses changes related to menopause, osteoporosis, cardiovascular issues
    • HRT has risks and rewards and must be considered for age, osteoporosis, cardiovascular diseases, breast or endometrial cancers.

    Breast Cancer Risk

    • Minimal if initiated post-menopause for the first seven years
    • Should be initiated immediately after menopause for minimizing cancer risk.
    • Women with pre-mature menopause may benefit from HRT after menopause.

    Endometrial Cancer Risk

    • Reduced by adding progesterone alongside estrogen alone.
    • Given first 25 days of the month and progesterone the last 10 to 14 days for those with a full uterus.
    • Estrogen alone is acceptable for patients who have undergone a hysterectomy.
    • HRT dose should be the smallest amount to mitigate symptoms.

    Adverse Effects

    • Uterine bleeding - a common, but serious, symptom that may signal endometrial cancer
    • Breast cancer: risk increases with prolonged therapy, but minimized with shortest therapy
    • Endometrial cancer: Risk increases with dose and duration, but minimization is possible with progesterone addition
    • Other conditions: nausea, breast tenderness, migraines, gallstones, HTN, estrogen-dependent cancers, undiagnosed vaginal bleeding, risk of thromboembolic disorders, liver disease, smoking are contraindications to initiating estrogen therapy.

    Estrogen Inhibitors

    • Tamoxifen: is a partial agonist at the estrogen receptor. Works by binding estrogen/receptor co-activators and reducing breast cancer risk in high risk patients.
    • Tamoxifen is an anti-estrogenic agent in breast tissue but a mild estrogenic effect in the endometrium.

    Other Inhibitors

    • Letrozole and Exemestane are aromatase inhibitors
    • Aromatase inhibitors reduce estrogen production by blocking aromatase, an enzyme that converts androgens to estrogen.

    Ovulation Inducers (Clomiphene Citrate)

    • Partial estrogen receptor agonist
    • Inhibits estrogen actions
    • Elevates LH and FSH levels
    • Used for PCOS treatment
    • Can cause ovarian enlargement
    • Contraindicated in patients with enlarged ovaries.

    PCOS Mechanism

    • Genetic predisposition to excess ovarian androgen secretion
    • Polycystic ovary, hirsutism, elevated testosterone and insulin levels, insulin resistance and hyperinsulinemia, anovulation
    • Insulin resistance may be influenced by genetics and dietary factors

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    Description

    This quiz covers essential topics related to estrogens, including their types, sources, and effects on health, particularly breast cancer risk. It also delves into the ovarian cycle, detailing the roles of different cells and hormone fluctuations during various stages of the cycle. Understanding these principles is crucial for comprehending female reproductive biology.

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