PROGESTERONE — Drug Presentation (OBG Nursing)

1. Introduction

2. Classification

• By source:
  • Natural/bioidentical progesterone (micronized progesterone)
  • Synthetic progestins (progestogens) - e.g., 17α-hydroxyprogesterone caproate (17-OHPC), medroxyprogesterone acetate, megestrol acetate, norethindrone, dydrogesterone
• By chemical class:
  • Progesterone derivatives - progesterone, hydroxyprogesterone caproate, medroxyprogesterone acetate, megestrol acetate
  • 17-Ethinyl-testosterone (estrane) derivatives
  • 19-Nortestosterone derivatives - norethindrone, desogestrel, levonorgestrel
• By use: Hormone replacement/luteal support, contraceptive progestin, tocolytic/preterm-birth-prevention agent, antineoplastic (megestrol), antagonist (mifepristone - antiprogestin) (Katzung's Basic and Clinical Pharmacology, 16th ed., Table 40-2)

3. Dose

• Vaginal micronized progesterone (preterm birth prevention in short cervix): 90-200 mg vaginal gel/suppository once daily
• 17-Hydroxyprogesterone caproate (17-OHPC): 250 mg IM once weekly, usually started 16-20 weeks until 36 weeks gestation, for women with prior spontaneous preterm birth
• Oral micronized progesterone (luteal phase support/menopausal symptoms): 100-200 mg/day (e.g., typical single-agent dose ~100 mg/day)
• Progesterone injection (IM, for amenorrhea/dysfunctional bleeding): 25-100 mg IM as directed (Creasy & Resnik's Maternal-Fetal Medicine; Berek & Novak's Gynecology)

4. Route

• Intramuscular (IM) - progesterone in oil, 17-OHPC
• Vaginal - gel, suppository, insert (preferred for preterm birth prevention; achieves high local uterine concentration with fewer systemic effects)
• Oral - micronized progesterone (high first-pass metabolism, so oral formulations must be specially micronized to be effective)
• Intrauterine - progesterone-releasing IUD

5. Frequency

• IM 17-OHPC: once weekly
• Vaginal progesterone: once daily (usually at bedtime)
• Oral micronized progesterone: once or twice daily
• Injectable progesterone (short acting): plasma half-life is very short (~5 minutes), so it must be given regularly per protocol, not as a single dose, to maintain effect

6. Mechanism of Action

• Converts proliferative endometrium into secretory endometrium, preparing it for implantation
• Decreases myometrial excitability and contractility (reduces uterine contractions, hence its use in preterm labor prevention)
• Suppresses the hypothalamic-pituitary axis (decreases GnRH pulse frequency), contributing to its contraceptive effect
• Thickens cervical mucus, making it impermeable to sperm
• Raises basal body temperature (thermogenic effect on hypothalamus)
• Increases ventilatory drive/response to CO2
• Promotes glycogen storage and mild insulin resistance, favors fat deposition (Katzung's Basic and Clinical Pharmacology, 16th ed., "Mechanism" and "Effects of Progesterone" sections)

7. Pharmacokinetics

• Absorption: Rapidly absorbed by all routes
• Half-life: Very short in plasma (~5 minutes) for natural progesterone; hence needs sustained-release formulations (oil-based IM, micronized oral, vaginal gel) for clinical use
• Metabolism: Almost completely metabolized in a single pass through the liver (extensive first-pass effect) - metabolized to pregnanediol, conjugated with glucuronic acid
• Excretion: Excreted in urine as pregnanediol glucuronide (used clinically as an index of progesterone secretion)
• Duration of action varies by formulation: Progesterone (IM) ~1 day; hydroxyprogesterone caproate 8-14 days; medroxyprogesterone acetate tablets 1-3 days, depot injection 4-12 weeks (Katzung's Basic and Clinical Pharmacology, 16th ed.)

8. Drug Interactions

• Hepatic enzyme inducers (rifampin, phenytoin, carbamazepine, some antiretrovirals, St. John's Wort) increase progesterone/progestin metabolism, reducing efficacy
• CYP3A4 inhibitors (ketoconazole, certain macrolides) may increase progesterone levels/toxicity
• Aldosterone/mineralocorticoid receptor competition - progesterone competes with aldosterone at the renal tubule; concurrent use with antihypertensives or diuretics needs monitoring of blood pressure and electrolytes
• Bromocriptine and other dopamine agonists: progesterone may alter their effect on prolactin
• Anticoagulants (warfarin): progestins may alter clotting factor synthesis, warranting INR monitoring
• Acitretin and other retinoids may reduce efficacy of progestin-only contraceptives (Fitzpatrick's Dermatology)
• Concurrent estrogen therapy alters risk profile (thrombosis, hepatic effects) - relevant in combined hormone therapy

9. Indications

• Prevention of recurrent spontaneous preterm birth in singleton pregnancy with prior preterm birth (17-OHPC IM or vaginal progesterone)
• Short cervix on ultrasound in current pregnancy - vaginal progesterone reduces risk of preterm birth <34 weeks
• Threatened abortion / luteal phase defect support
• Assisted reproductive technology (ART) - luteal phase support after IVF
• Dysfunctional uterine bleeding / amenorrhea (progestin withdrawal test)
• Contraception (progestin-only pills, implants, injectables, IUD)
• Endometriosis and endometrial hyperplasia management
• Menopausal hormone therapy (combined with estrogen, to protect endometrium)
• Some use in appetite stimulation (megestrol) and hormone-sensitive cancers (as antagonist context) (Creasy & Resnik's Maternal-Fetal Medicine; Berek & Novak's Gynecology)

10. Contraindications

• Known or suspected pregnancy-unrelated hormone-sensitive breast or genital tract cancer
• Active or history of thromboembolic disorders (DVT, PE, stroke) - especially with estrogen-progestin combinations
• Undiagnosed abnormal vaginal bleeding
• Severe hepatic disease/impairment (impaired metabolism of the hormone)
• Known hypersensitivity to progesterone or its vehicle (many injectable formulations are in oil - caution with peanut oil allergy for some brands)
• Missed abortion or active liver tumors
• Used with caution in women with a history of depression, migraine, or fluid retention/cardiac or renal disease (mineralocorticoid-related sodium/water retention)

11. Specific Side Effects

• Local: Pain, irritation, or sterile abscess at IM injection site (17-OHPC injections are notoriously painful)
• Systemic/hormonal: Breast tenderness, bloating, mood changes/depression, fatigue, dizziness, headache
• Metabolic: Mild insulin resistance, weight gain, fluid retention (due to aldosterone antagonism causing compensatory aldosterone rise)
• Reproductive: Irregular vaginal bleeding/spotting, amenorrhea with prolonged use
• Respiratory: Increased ventilatory drive (mild hyperventilation sensation)
• Thermoregulatory: Mild rise in basal body temperature
• Rare/serious: Thromboembolism (more with synthetic progestins/combined with estrogen), hepatic dysfunction, allergic/anaphylactoid reaction to injection vehicle
• Obstetric-specific: slightly increased risk reported with vaginal progesterone use is generally minimal; with 17-OHPC, injection-site reactions are the most common complaint prompting non-adherence

12. Nurse's Role

• Before administration:
  • Verify prescriber's order - drug, dose, route, frequency, and gestational indication
  • Confirm pregnancy status/gestational age and obtain baseline vital signs, weight
  • Assess for contraindications (history of thromboembolism, liver disease, undiagnosed bleeding, allergy)
  • Educate the patient on the purpose of therapy, expected duration (e.g., 17-OHPC continued until 36 weeks), and importance of adherence
• During administration:
  • For IM 17-OHPC: use Z-track technique in a large muscle (gluteal), rotate injection sites, warm the vial to room temperature before injecting to reduce pain and viscosity issues
  • For vaginal progesterone: teach correct insertion technique, timing (usually bedtime), and to avoid leakage by lying down briefly after insertion
  • Maintain aseptic technique for all routes
• Monitoring:
  • Monitor for signs of thromboembolism (leg pain/swelling, chest pain, shortness of breath), allergic reaction, and injection-site complications
  • Monitor fetal well-being and signs of preterm labor despite therapy (progesterone reduces but does not eliminate risk)
  • Watch for mood changes, fluid retention, or abnormal bleeding and report to physician
• Patient education:
  • Explain that missed doses reduce effectiveness; reinforce adherence, especially for weekly IM injections
  • Advise reporting any unusual bleeding, severe headache, visual changes, leg swelling, or chest pain immediately
  • Reassure regarding common, self-limiting effects (soreness at injection site, mild bloating)
  • Provide emotional support, as patients on progesterone therapy for recurrent pregnancy loss/preterm birth often have high anxiety
• Documentation: Record site, dose, batch number (for injectables), and patient response after every administration; document patient teaching provided

PROGESTERONE — Drug Presentation (OBG Nursing, Concise)

• Natural: micronized progesterone
• Synthetic progestins: 17-OHPC, medroxyprogesterone acetate, norethindrone, dydrogesterone

• Vaginal micronized progesterone: 90-200 mg/day
• 17-OHPC: 250 mg IM weekly
• Oral micronized: 100-200 mg/day

• Enzyme inducers (rifampin, phenytoin, carbamazepine) ↓ efficacy
• CYP3A4 inhibitors ↑ levels
• Competes with aldosterone → fluid retention with antihypertensives/diuretics
• Alters warfarin effect

• Verify order, confirm pregnancy status, screen contraindications
• Z-track IM technique, rotate sites; teach vaginal insertion technique
• Monitor for thromboembolism signs, bleeding, allergic reaction
• Educate on adherence (esp. weekly IM), reportable symptoms
• Document site, dose, response