Steroid Hormones Comprehensive Notes

The Function & Effect of Sex Steroid Hormones

Objectives

  • Explain the contribution of the HPA (Hypothalamic-Pituitary-Adrenal) and gonadal axis to the synthesis of sex steroids.
  • Explain the physiology & pathophysiology of the adrenal & gonadal steroids in disease states.
  • Recognize the different structures & functions of sex steroids.
  • Expound on the synthesis & physiology of the various sex hormones (androgens & estrogens).
  • Elucidate the pharmacologic use and adverse effects of the sex steroids & contraceptives.

Steroid Hormones

  • Natural steroid hormones are produced in the gonads (testes and ovaries) and adrenal cortex.
  • They are released into the bloodstream and carried by either corticosteroid-binding globulin or sex hormone-binding globulin.
  • Before Puberty:
    • FSH (Follicle Stimulating Hormone) & LH (Luteinizing Hormone) secretion is high in newborns but falls to low levels in a few weeks.
    • Neuroendocrine brake imposed by glutamate, GABA, and neuropeptide Y.
    • Adrenarche occurs between 6-8 years old, followed by gonadarche (approximately one year before menarche in females).
    • The precursors to sex steroids are made and released by the adrenal cortex.

Plasma Gonadotropins

  • Graph depicting FSH and LH levels from birth to menopause.
    • FSH: High at birth, decreases during infancy and childhood, increases during puberty, then declines after reproductive years and increases during menopause.
    • LH: Similar pattern to FSH.

Corticosteroids

  • Hypothalamus releases CRH leading to pituitary release of ACTH. Adrenal cortex stimulates synthesis of:
    • Zona glomerulosa: Mineralocorticoids (aldosterone).
    • Zona fasciculata: Glucocorticoids (cortisol and corticosterone).
    • Zona reticularis: Androgens (dihydroepiandrosterone; androstenedione).
  • Adrenal medulla: Preganglionic fibers stimulate the liberation of epinephrine and norepinephrine.
  • The adrenal cortex MUST BE STIMULATED HORMONALLY (ACTH).

Corticosteroids

  • Free cholesterol is the preferred precursor, although the adrenal cortex can form cholesterol from acetylCoA.
  • The rate-limiting step in corticosteroidogenesis is the side-chain cleavage (SCC) of cholesterol to pregnenolone by 20,22-desmolase, also known as cholesterol desmolase, P450scc, or CYP11A1.
  • Pregnenolone is the common precursor of all steroid hormones.

Steroid Hormone Synthesis Pathways

  • Diagram showing the synthesis pathways for mineralocorticoids, glucocorticoids, and androgens/estrogens from cholesterol.
    • Key enzymes: 3β-Dehydrogenase, 17α-Hydroxylase (P450c17), 21β-Hydroxylase (P450c21), 11β-Hydroxylase (P450c11), Aromatase.

Onset of Puberty

  • At puberty:
    • Brain maturation increases GnRH secretion that starts as nocturnal surges, progressing to daily pulsatile secretion.
    • Decreased sensitivity of gonadotropin to negative feedback.
    • During late puberty, pulsatile secretion of LH and FSH increases during sleep.
    • Stimulate a rise in sex steroid secretion.

Sex Steroids

  • Hypothalamus releases GnRH, stimulating the pituitary to release LH/FSH which then affect the Gonads to produce sex steroids, Inhibin, and Activin.

Plasma Gonadotropins

  • Graph depicting FSH and LH levels from birth to menopause . The graph shows the cyclical change from birth to menopause.

Feedback Control of Anterior Pituitary

  • Factors affecting the hypothalamus:
    • Psychological stress, exercise, emotions, pain, cold exposure, sleep, hemorrhage, hypoglycemia, infections, trauma, toxins, circadian rhythms, menstrual cycle.
  • Hypothalamus releases GnRH, stimulating the pituitary to release FSH and LH (gonadotropins).
  • Gonadotropins act on the gonads to produce sex steroids and gametes (sperm or ova).
  • Inhibin provides negative feedback.

Neurotransmitters & Releasing Hormones

  • Hypothalamus releases:
    • GnRH (Gonadotropin-Releasing Hormone).
    • GHRH (Growth Hormone-Releasing Hormone).
    • PRF (Prolactin-Releasing Factors).
    • TRH (Thyrotropin-Releasing Hormone).
    • CRH (Corticotropin-Releasing Hormone).
    • PIF (Prolactin-Inhibiting Factor) aka Dopamine.
  • Anterior Pituitary Hormones:
    • FSH, LH, GH, TSH, ACTH, PRL, β-LPH, β-END, α-MSH, CLIP
  • Target Organs:
    • Liver (IGFs), Thyroid (T4/T3), Adrenal Cortex (Corticosteroids), Mammary Gland, Testis, Ovary.

Estrogens

  • Estrogens include the natural hormones, semi-synthetic & synthetic (stilbene) agents.
  • Major estrogens produced by women are:
    • Estradiol (E2) (estradiol-17β): From ovary by the theca interna & the granulosa cells of the follicles of nonpregnant females, adipocytes.
    • Estrone (E1): Primarily during menopause.
    • Estriol (E3) primary estrogen & Estetrol (E4) secondary estrogen of pregnancy.

Follicle Development

  • Diagram showing the stages of follicle development.
    • Primordial follicle, primary follicle, preantral follicle, antral follicle, preovulatory follicle.
    • Ovulation: Mature follicle releases ovum.
    • Corpus luteum forms, degenerating corpus luteum

Theca and Granulosa Cell Function

  • Theca cells:
    • LH stimulates cholesterol conversion to androstenedione.
  • Granulosa cells:
    • FSH stimulates aromatase, which converts testosterone to estradiol.

Follicular and Luteal Phases

  • Diagram showing steroidogenesis in ovaries, liver, adrenal glands, breasts and placenta

Actions of Estrogens

  • On sexual organs (primary and secondary sexual characteristics).
    • Ovaries: Stimulate follicular growth; small doses cause an increase in weight of ovary; large doses cause atrophy.
    • Uterus: Endometrial growth.
    • Vagina: Keratinization of epithelial cells with thickening and stratification of epithelium.
    • Cervix: Increase of cervical mucous with a lowered viscosity (favoring sperm access).

Actions of Estrogens

  • Development and maintenance of internal (fallopian tubes, uterus, vagina), and external genitalia.
  • Skin: Increase in vascularization, development of soft, textured, and smooth skin.
  • Bone: Increase osteoblastic activity.
  • Electrolytes: Retention of Na^+, Cl^- and water by the kidney.
  • Cholesterol: Hypocholesterolemic effect.

Female Reproductive Anatomy

  • Diagram showing the anatomy of the female reproductive system, including ovaries, fallopian tubes, uterus, cervix, and vagina.

Menstrual Cycle

  • Diagram illustrating the thickening of uterus lining. Egg travels to uterus if not fertilised, dissolves

Menstrual Cycle

  • Duration approximately 28 days.
  • Menstruation:
    • Day 1-4/5. Day 1 is the first day of menstruation.
    • Secretion of estrogen and progesterone are at their lowest.
    • Ovaries contain only primary follicles.

Follicular Phase

  • Lasts from day 1 to about 13.
  • Under the influence of FSH, several vesicular follicles begin to enlarge.
  • Follicles become increasingly sensitive to FSH.
  • Estrogen stimulates the production of FSH receptors on the granulosa cells which causes a positive feedback effect as it makes them more sensitive to FSH and after 5-6 days one follicle called the dominant or primary follicle develops more rapidly.
  • Toward the end of the phase, sensitivity of FSH receptors increases.
  • FSH and estradiol stimulate production of LH receptors in graafian follicle theca cells.

Follicular Phase Continued

  • FSH stimulates granulosa cells to convert androgens from theca cells into estradiol causing a rapid rise in estradiol.
  • Negative feedback on LH and FSH mostly by inhibin A and B causes atresia of nondominant follicles.

Follicular Phase Continued

  • Hypothalamus increases frequency of GnRH pulses and increases the ability of anterior pituitary to respond to GnRH to increase LH secretion despite estrogen negative feedback.
  • Positive feedback loop in dominant follicle: Increasing estrogens from the follicle plus the increasing LH from the anterior pituitary gland act together to cause proliferation of the follicular thecal cells and increase their secretion as well.
  • When estradiol remains elevated for a sustained period of time (then drops), the pituitary releases a midcycle LH surge.
  • LH surge begins 16-24 hours before ovulation and triggers ovulation.

Hormone Levels During Menstrual Cycle

  • Graphs showing estradiol, LH, FSH, and progesterone levels during the menstrual cycle.
    • Estradiol peaks during the follicular phase, triggering the LH surge.
    • Progesterone rises during the luteal phase.

Ovulation

  • Wall of Graafian follicle ruptures releasing egg.
  • Occurs on Day 14.

Ovulation

  • Image of egg being retrieved from the ovary using surgical instruments.

Luteal Phase

  • LH stimulates formation of the empty follicle into the corpus luteum.
  • Corpus luteum secretes both:
    • Progesterone: Plasma concentration rapidly rises, exerting negative feedback on LH and FSH.
    • Inhibin A: Suppresses FSH secretion, decreasing towards the end of the luteal phase.

Luteal Phase

  • Corpus luteum regresses unless fertilization occurs, leading to decreased estradiol and progesterone.
  • Withdrawal of estradiol and progesterone causes menstruation.

Cyclic Changes in the Endometrium

  • Proliferative Phase:
    • Ovary is in the follicular phase.
    • Estradiol stimulates growth of the stratum functionale layer of the endometrium, promotes development of spiral arteries, and stimulates production of receptor proteins for progesterone.

Uterine Layers

  • Diagram of Endometrium, Myometrium, and Perimetrium and various arterial structures.

Cyclic Changes in the Endometrium

  • Secretory Phase:
    • Ovary is in the luteal phase.
    • Progesterone stimulates development of uterine glands, which become engorged with glycogen.
    • Endometrium becomes thick, vascular, and spongy.
    • Cervical mucus thickens and becomes sticky.

Cyclic Changes in the Endometrium

  • Menstrual Phase:
    • Progesterone withdrawal and/or PG-mediated inflammation causes constriction of spiral arteries.
    • Necrosis and sloughing of the functional layer of the endometrium occurs.
    • Lasts 1-5 days.

Cycle of Ovulation and Menstruation Events

  • Endometrium thickness fluctuates in phases. Both Ovarian and Gonadotropin secretions also change in phases with the Menstrual cycle. The graph depicts a cycle, ending where is begins, around 28 days.

Endocrine Control of the Ovarian Cycle

  • Diagram showing hormone feedback loop from the hypothalamus, anterior pituitary, and ovaries.
    • GnRH stimulates FSH and LH release.
    • Estradiol and progesterone provide negative feedback.
    • During ovulation, estradiol can provide positive feedback, causing an LH surge.

Estrogen Therapeutic Uses

  • Exogenous estrogens are used as hormone-replacement therapy for hypogonadism or menopause, in oncology, as contraceptives, for acne control, endometriosis, and uterine bleeding.
  • Acute profuse bleeding: high dose IV estrogen (Premarin 25 mg IV up to four doses).

Forms of Estrogens

  • Estradiol (oral): micronized prep- Estrace.
  • Estradiol (topical): Divigel, Estrogel.
  • Estradiol (transdermal): Alora, Climara, Vivelle.
  • Estradiol (vaginal): Estrace, Estring, Femring, Vagifem.
  • Synthetic Estradiol: Ethinyl Estradiol (EE).
  • Estrone based: Esterified estrogens (Menest) & Estropipate (Ogen, Ortho-Est).
  • Conjugated estrogens: equine source (Premarin) plant sources (Cenestin).

Premarin

  • Most commonly prescribed HRT and is #72 of the top 100 medications.
  • Premarin is derived from Pregnant Mare’s Urine.

Forms of Estrogens

  • Transdermal Estradiol: prevents high levels from entering liver, decreasing effects on protein synthesis, lipoprotein profiles, and triglycerides.
  • Topical creams –Estrasorb or gel- Estrogel.
  • Vaginal rings: Estring, Femring, Nuvaring.
  • Vaginal tablet: Vagifem

Forms of Estrogens

  • Intramuscular Injection:
    • Estradiol Valerate (Delestrogen).
    • Estradiol cypionate (Depo-estradiol).
  • NEW: Synthetic Estetrol: plant-based estrogen.

Side Effects of Estrogens

  • Heavy menstrual bleeding/cramping.
  • Breakthrough bleeding or spotting.
  • Breast tenderness.
  • Fluid retention, weight gain, increased fat storage.
  • Depression/anxiety.
  • Glucose intolerance, Insulin Resistance.
  • Stimulates growth of Fibroids.
  • Worsens Endometriosis.
  • Vomiting, cramping, bloating.
  • Increased risk of endometrial cancer.
  • Loss of scalp hair, growth of facial & body hair.
  • Eye problems.
  • Gall bladder disease.
  • Pancreatitis.
  • Melasma- dark skin patches, usually on face.

Cancer Related Effects

  • RR of breast cancer increases to 1.1-1.2
  • Cervical cancer increased 2 fold but only in those using > 5 years.
  • Doubling of liver cancer in those using > 4-8 yrs.
  • Decreases ovarian, endometrial & colorectal cancer.
  • 5-15 fold increase in Endometrial cancer with use of unopposed estrogen!
  • If combined with a progestin, the risk is decreased to 50% @1yr and 80% @ 10yrs

Clomiphene

  • Clomiphene (GNRH Agonist-Ovulation Simulant).
  • An estrogen partial agonist at receptors & inhibits estradiol’s negative feedback on gonadotropins → increases the release of FSH and LH which will result in follicular maturation & ovulation which increases the chance of multiple pregnancy.
  • SE: ovarian enlargement, vasomotor flushes, and visual disturbances & Thrombosis risk.

Other Ovulation Stimulants

  • Choriogonadotropin alpha (Ovidrel).
  • Chorionic Gonadotropin (Lupron, Pregnyl, Novarel).
  • Follitropin Alpha: FSH, Gonal–F.
  • Follitropin Beta: FSH, (Follistim AQ) + Lutropin Alpha (Luveris).
  • Urofollitropin (Bravelle).
  • Gonadotropins (FSH and LH, menotropins-Menopur, Pergonal, Repronex).

Ovulation Stimulants

  • Are either delivered SC abdominally or IM on the upper outer quadrant using prefilled pens or syringes or in ampules that must be reconstituted.
  • Injection site complications, CNS (depression, fatigue, HA).
  • Ovarian hyper-stimulation syndrome.

Aromatase Inhibitors

  • Aromatase is a cytochrome P450 enzyme that catalyzes the conversion of adrenal androgen androstenedione to estrone & estradiol in both pre- and postmenopausal women.
  • The reaction occurs in the liver, muscle, adipose, and breast tissue.
  • In post-menopausal women, aromatization is responsible for the majority of circulating estrogen.

Aromatase Inhibitors

  • Drugs may be steroidal: Exemestane (Aromasin) or non-steroidal: Anastrozole (Arimidex) , Letrozole Femara).
  • Estrogen deprivation through aromatase inhibition is an effective way to increase FSH release and increase ovulation.

Ospemifene

  • Ospemifene (OSPHENA)…A SERM.
  • For Dyspareunia.
  • 60 mg Tab only once daily with food.
  • Contraindicated in estrogen-dependent neoplasia, pregnancy, DVT/PE, MI and history of stroke or abnormal genital bleeding or with severe hepatic impairment.
  • SEs: Hot flashes, hyperhidrosis, muscle spasms, vaginal discharge.

Danazol

  • Danazol (DANOCRINE).
  • Derivative of Ethisterone with weak progestational, androgenic, and glucocorticoid activity.
  • Inhibits the midcycle surge of LH and FSH. Inhibits P450scc, P450c17, P450c11, and P450c21, 3β & 17α-hydroxysteroid dehydrogenase but not aromatase.
  • Half-life of 15 hours.
  • Major use is for endometriosis.

Danazol Continued

  • Dosing: Can use up to 600 mg/d for 1 month, → 400 mg/d → 200mg/d. The usual starting dose is 400 mg bid then titrate downward until amenorrheic for 3-6 mths.
  • Fibrocystic breast disease, menorrhagia & mastalgia.
  • BBW: thromboembolic events, pregnancy, hepatic effects, intracranial hypertension.
  • Contraindicated in hepatic, renal & cardiac dysfunction & Androgenic effects!

Hormonal Contraception Overview

  • Diagram showing the mechanism of action of oral contraceptives and other hormonal agents.

Progesterone-Progestogens, Progestins

  • Natural hormone secreted by the corpus luteum and the placenta (a C-21 steroid).
  • Intermediate in steroid biogenesis in all tissues that produce steroids (testes, ovary, adrenal).
  • Complements the action of estrogen on primary and secondary sex characteristics.
  • Progesterone has T_{1/2} of 20 minutes.
  • Metabolized by the liver at C5 and C20.

Steroidogenesis

  • Same steroidogenesis diagram from earlier slides, showing progesterone as an intermediate.

Progesterone Effects

  • Stimulates lipoprotein lipase.
  • Increases basal insulin, increases glycogen storage in the liver.
  • Development of secretory apparatus in the breast.
  • Participates in LH surge and causes follicular and endometrial maturation.
  • Rise during the luteal phase inhibits GnRH, therefore inhibiting further ovulation.
  • Increases in body temperature, increases excretion urinary nitrogen.
  • Decreases Na^+ reabsorption (except drospirenone) & certain plasma AA’s.

Therapeutic Uses of Progesterone

  • Hormone replacement therapy.
  • Prolongs anovulation and amenorrhea in the treatment of dysmenorrhea, endometriosis, and bleeding disorders when estrogens are contraindicated.
  • May relieve hot flashes.
  • Oral contraceptives: norgestrel, levonorgestrel, norethindrone, norethindrone acetate, norethynodrel, ethynodiol diacetate, desogestrel, and norgestimate.

Progestogens List

  • List of Progestogen medications, including:
    • Desogestrel, dienogest, drospirenone, etonogestrel, levonorgestrel, medroxyprogesterone, norelgestromin, norethindrone, norgestimate, norgestrel, progesterone.

Progesterone Routes, Half-Lives, and Activities

  • Table of various progestins and their activity levels

Progesterone Side Effects

  • Injectable medroxyprogesterone acetate has been associated with an increased risk of osteoporosis.
  • 19-nortestosterone derivatives have androgenic activity & can increase the ratio of LDL to HDL cholesterol & cause acne & hirsutism.
  • Drospirenone-containing OCPs (YAZ, YASMIN, etc), may increase potassium (K+) levels.

Progestin: Drospirenone

  • Decreases bloating, PMS symptoms, acne, weight gain due to antimineralocorticoid activity of drospirenone which is equivalent to 25 mg of spironolactone & therefore has K+ sparing properties so monitor K+ if taking ACEI, ARBS, K+ sparing diuretics or aldosterone antagonists.
  • Monitor potassium w/ Safyral, Yasmin, Yaz, Loryna, Ocella, Syeda, Beyaz, and others.
  • May have an increased risk for blood clots vs other progestin-containing pills.
  • Avoid use if kidney, liver, or adrenal gland disease.

Progesterone: Prometrium

  • Used For:
    • 1. Prevention of estrogen-induced endometrial hyperplasia- 200mg daily.
    • 2. Secondary physiologic amenorrhea-400mg po daily or 4%-8% gel qod. Vaginal bleeding should occur within 3-7 days post last dose.
    • 3. Assisted reproduction for infertile women- 8% gel.

Prometrium MOA and Contraindications

  • MOA: inhibits gonadotropin release & converts the proliferative endometrium to secretory endometrium.
  • Contraindicated in hormone-dependent neoplastic conditions or for those with cardiac & clotting risks (DVT,PE)-BBW or with abnormal vaginal bleeding.
  • Oral form: avoid if hypersensitivity to progesterone or any component of the formulation including peanuts/peanut oil.
  • IM form: sesame oil/seeds.
  • Intravaginal gel: palm oil.

Prometrium Black Box Warning

  • BBWs: WHI-in postmenopausal women 50-79 yo, increased breast cancer & probable dementia(>65), stroke, PE, MI & DVT w/ conjugated estrogens & medroxyprogesterone acetate.
  • Monitor INR w/warfarin.
  • Most common side effects of oral formulation are breast tenderness & headache.

Antiprogestin

  • Mifepristone is a progesterone antagonist with partial agonist activity. Administration of this drug to females early in pregnancy results in abortion of the fetus due to the interference with progesterone and the decline in human chorionic gonadotropin.
  • The major adverse effects are significant uterine bleeding and the possibility of an incomplete abortion. However, administration of misoprostol after a single oral dose of mifepristone effectively terminates gestation.
  • 200 mg oral Mifepristone followed by one or two 800 mcg doses of misoprostol vaginally or buccally for pregnancy loss or abortion.
  • Misoprostol (Cytotec) a prostaglandin E1 analog causes cervical ripening and uterine contractions.

Hormone Effects Fluid and Sodium Regulation

  • Diagram showing the complex control of fluid and sodium balance and the multiple ways in which estradiol (E2) and progesterone (P4) may influence these processes.

Contraception Statistics

  • Approximately 6 million females become pregnant in the U.S. each year.
  • 37% of these pregnancies are unintended.
  • Teen births account for 11% of all births in U.S.
  • About 50% of all unintended pregnancies end in abortion and 40% occur in sexually active couples who claim they used some method of contraception.
  • ACOG in 2019 recommended OTC access to all hormonal contraceptives.

Contraceptives

  • Oral (1960).
  • Parenteral/Implanted.
  • States that allow Pharmacists to prescribe hormonal birth control ( list follows on next slides).
    • Goals of Contraception: For pregnancies to be planned and desired & Protection from sexually transmitted diseases.

Contraceptive Methods

  • Abstinence.
  • Family Planning.
  • Withdrawal Method.
  • Barrier Method: Vaginal spermicide, male condom, female condom, sponge, cervical caps, diaphragm.
  • Hormonal Contraception: Combined oral contraceptives (COCs), transdermal, ring, injectable, subdermal implants, intrauterine device (IUD).
  • Emergency contraception.
  • Tubal Ligation or Vasectomy.

Contraception Use Statistics

  • Chart showing the percentage of women using different types of contraception. Most common are Pill, Tubal Sterilization, Male Condom, and IUDs.

Which Method To Choose

  • Highly individualized.
  • Patient preference.
  • Financial considerations.
  • Effectiveness and Length of time to remain non-fertile.
  • STD protection.
  • Contraindications.
  • Other benefits besides contraception.

Nonpharmacologic Therapy

  • Periodic Abstinence also known as the rhythm method.
  • Avoiding sexual intercourse during the days of the menstrual cycle when conception is likely to occur.
  • Drawbacks = high pregnancy rates and avoidance of intercourse for several days during cycle.

Periodic Abstinence SBT Chart Diagram.

  • Text provides instructions for ovulation predictions methods via tracking body temperature.

Nonpharmacologic Therapy

  • Barrier Techniques: Effectiveness depends on motivation to use them consistently and correctly.
  • Condoms, diaphragms, cervical caps, and sponges (Today®).
  • Higher failure rates than most hormonal contraceptives.

Condoms

  • Male condoms are made of latex or polyurethane only (not lamb or sheepskin) for HIV protection.
  • Use water or silicone base lubricants only.
  • Female condom - Reality®: Lubricated, loose-fitting polyurethane sheath closed at one end with flexible rings.

Nonpharmacologic Therapy

  • Spermicides – nonoxynol-9: Chemical surfactant that destroys sperm cell walls and act as barriers that prevent sperm from entering the cervical os.
  • CDC and WHO do not promote products containing nonoxynol-9 because It increases the risk of transmission of HIV by causing small disruptions in the vaginal epithelium if used more than twice per day.

Nonpharmacologic Therapy

  • Diaphragm w/spermicide.
  • Requires a prescription; most need to be fitted, but new CAYA is single size.
  • May be inserted up to 6 hours before intercourse & leave in for 6 hrs after sex.
  • Not recommended to be left in place for more than 24 hours due to the risk of Toxic shock syndrome.

Nonpharmacologic Therapy

  • Cervical cap - FemCap® soft deep cup that is smaller than a diaphragm, and fits over the cervix like a thimble. Requires a prescription.
  • Should be filled with spermicide prior to insertion; can be inserted 6 hours before intercourse and should be removed for at least 6 hours after intercourse.
  • High failure rates.

Contraceptive Barriers

  • Cervical Cap vs. Diaphragm.

Hormonal Contraceptive Types

  1. (CHC & COCs) Combination of estrogens & progestins.
    • Combination further divided into 3 forms: Monophasic, Biphasic, and Triphasic. (definitions below).
  2. Continuous progestin only therapy

Mechanism of Action

  • Combination products: Selective inhibition of pituitary function results in: Estrogen component inhibits FSH secretion, preventing the development of dominant follicle & therefore ovulation. Progestin component decreases GnRH pulses by inhibiting LH surge preventing ovulation.Thickens cervical mucus, & atrophies endometrium, ↓ motility & secretion in uterine tubes & can decrease sperm motility.
  • Progestin only: May not always inhibit ovulation (40% will continue to ovulate) and therefore relies on the other factors.

Endocrine Control of the Ovarian Cycle

  • Contraceptives containing active ingredients can create a hormone feedback loop that inhibits the hypothalamus from stimulation the anterior pituitary. If the Anterioir pituitary is inhibited, then it cannot stimulate the Ovaries.

Components in Birth Control Pills

  • Estrogen : Ethinyl Estradiol (EE), Mestranol, or Estetrol (E4).
  • Progestin: Norethindrone, Norethindrone acetate, Ethynodiol diacetate, Levonorgestrel, Norgestrel , Desogestrel, Norgestimate, Drosperinone, or Norethynodrel.

Monophasic Contraceptives

  • Fixed ratio of estrogen to progestin delivered though 21 or 84 active pills followed by 1 week of placebo pills.
  • Exceptions: Mircette & Kariva, Lybrel, Camrese & Seasonique.
  • Examples: Loestrin, Levlen, Levora, Levlite, Desogen, Lo/Ovral, Ortho-Cept, Nordette, Demulen, Ovcon, Modicon, Zovia, Apri, Microgestin, Yasmin, Ortho-Cept, Levora, Alesse.

Monophasic Medications

  • Images of advertisements and boxes of drugs: LevlenⓇ 28 Tablets, Lo/OvralⓇ, and NordetteⓇ-28.

Lo Loestrin Fe

  • Loestrin FE 1/20 = ethinyl estradiol 0.02 mg (20 mcg) / norethindrone 1 mg.
  • Loestrin 24 FE consists of 24 white active tablets and 4 brown non-hormonal (placebo) tablets of 75 mg ferrous fumarate.

Nextstellis-New

  • 24 hormonal pink, 4 inert white pills. Contains first new estrogen in 50 years, Estetrol (produced from soybean plant source) with drospirenone.

Biphasic Contraceptives

  • Mainly named 10/11 and contain one estrogen concentration throughout active pills, and two progestin concentrations (one for 10 days, & another for 11 days).
  • Examples: Ortho-Novum 10/11, Nelova 10/11, Necon 10/11, Jenest-28, Mircette, Kariva.

Desogestrel/Ethinyl Estradiol Comparison

  • Medications: Kariva Desogestrel and Ethinyl Estradiol. Details for 1st and 21st dose over a 28-day dosing period in the third cycle.

Triphasil Advertisement

  • Images of advertisements and boxes of drugs: Trivora 28 Tablets, Triphasil-28, ORTHO TRI-CYCLEN Lo.

Triphasic Contraceptives

  • Examples: Ortho-Novum 7/7/7, Tri-Norinyl, Tri-Levlen, Triphasil, Trivora-28, Estrostep
  • Ortho-Tri-Cyclen Lo 28: 7 white tablets with 0.180 mg norgestimate & 0.035 mg ethinyl estradiol, 7 light blue tablets with 0.215 mg norgestimate & 0.035 mg ethinyl estradiol, 7 blue tablets: 0.250 mg norgestimate & 0.035 mg ethinyl estradiol, and 7 green tablets (inert placebo).

Pharmaceutical packaging of a Triphasic Contraceptive