Reading Resources on Recent Advances in Female Hormonal Contraception

1. Foundational Textbook Chapters

• Hormonal Contraception (block 3, p. 730) - covers all OC formulations, progestin pharmacology, steroid receptor pharmacology
• HORMONAL CONTRACEPTION (block 4) - detailed breakdown of: combined OCs (21/7 vs. 24/4 regimens, continuous-cycle methods), transdermal patches, vaginal rings, injectables, implants, progestin-only pills, and hormonal contraception in men
• Efficacy of Hormonal Contraception - failure rates, Pearl Index, real-world vs. perfect-use data

• Hormonal Contraception and Hormonal Contraception: A Brief History - excellent for mechanism of action, progestin classes, receptor selectivity, and pharmacokinetics

2. Clinical Practice Guidelines (Most Important)

U.S. Medical Eligibility Criteria for Contraceptive Use, 2024 (US MEC 2024)

• New combined OCs containing estradiol valerate and estetrol (E4) added as formulations
• Drospirenone-only pills (progestin-only, e.g., Slynd) added with their own eligibility categories
• Revised depot medroxyprogesterone acetate (DMPA) recommendations - reclassified to more restrictive categories in VTE-risk conditions
• New vaginal pH modulator (Phexxi) as a non-hormonal barrier method
• Updated recommendations for CKD subconditions, sickle cell disease, anticoagulant therapy

U.S. Selected Practice Recommendations for Contraceptive Use, 2024

UK Medical Eligibility Criteria (UKMEC 2025)

ACOG Committee Statement: Access to Contraception (2025)

3. Recent Peer-Reviewed Reviews (2023-2026)

On New Drug Formulations and Novel Estrogens

• Battipaglia C et al. (2024). "Insights on estetrol, the native estrogen: from contraception to hormone replacement therapy." Minerva Obstet Gynecol. PMID 39283289
  • Key points: E4 selectively activates nuclear ERa (not membrane ERa), giving it tissue-specific effects. Combined with drospirenone (marketed as Nextstellis/Lydisilka), it is commercially available since 2022. Lower hepatic impact, favorable hemostatic profile, potentially lower VTE risk than ethinyl estradiol (EE).
• Coelingh Bennink HJT et al. (2025). "The rediscovery of estetrol and its implications for estrogen treatment." Menopause. PMID 40586590 - PMC full text
  • Covers E4's high oral bioavailability, limited hemostatic effects, E4+DRSP registration worldwide as OC, and E4 for HRT expected in 2026.

On New Delivery Formats

• Al-Haddad S et al. (2023). "Advances in contraception: vaginal contraceptive rings." Ther Adv Reprod Health. PMID 37465002 - PMC full text
  • Compares the monthly ENG/EE ring (NuvaRing) vs. the 1-year segesterone acetate/EE ring (Annovera) - a major recent addition - covering efficacy, dosing, safety, and cost.

On Expanding Access and OTC Contraception

• Fox K, Lee R, Anderi E (2025). "Contraception Updates." Prim Care. PMID 40412904
  • Excellent primary-care oriented update; covers: Opill (norgestrel 75 mcg) as the first FDA-approved OTC daily oral contraceptive (approved 2023), drospirenone-only pill (Slynd), low-dose patch (Twirla), Annovera ring, Phexxi gel, and extended IUD use durations.
• Grossman D, Murphy EC (2025). "Expanding Access to Contraception." Obstet Gynecol Clin North Am. PMID 40320276
  • Covers OTC access, telehealth provision, pharmacist prescribing, and the significance of the FDA's Opill approval as a precedent.

On Special Populations

• Fidecicchi T et al. (2025). "Hormonal Contraception in Perimenopause: What to Consider to Guide the Choice." Semin Reprod Med. PMID 40972669
  • Addresses the unique challenge of contraception after age 40: balancing pregnancy risk with rising cardiovascular risk from EE; recommends preferring natural estrogens (E4, estradiol valerate) after 40 if estrogen is used.
• Cabre HE et al. (2024). "Effects of the Menstrual Cycle and Hormonal Contraceptive Use on Metabolic Outcomes, Strength Performance, and Recovery: A Narrative Review." Metabolites. PMID 39057670
  • Relevant for counseling active women and female athletes on how hormonal contraceptives interact with training adaptations and metabolism.
• Ricker EA et al. (2024). "Hormonal contraception and medical readiness for female service members." Am J Obstet Gynecol. PMID 38810770
  • Covers contraceptive choice and safety in a high-demand occupational setting.

On Cochrane-Level Evidence for Specific Indications

• Schroll JB et al. (2023). "Combined oral contraceptive pill for primary dysmenorrhoea." Cochrane Database Syst Rev. PMID 37523477 - systematic review on efficacy for pain management.
• Ma S, Song SJ (2023). "Oral contraceptives containing drospirenone for premenstrual syndrome." Cochrane Database Syst Rev. PMID 37365881

4. Online Reference Tools (For Ongoing Learning)

Summary of Key Advances to Focus On

1. Estetrol (E4) - a natural fetal estrogen, now in combined OCs (with drospirenone); potentially lower VTE and hepatic impact than EE-based pills
2. Drospirenone-only pill (Slynd) - a progestin-only pill with a 24-hour missed-dose window (vs. 3 hours for norethindrone), improving adherence
3. Opill (norgestrel 75 mcg) - first OTC oral contraceptive approved by FDA (2023), expanding access without prescription
4. Annovera ring (SA/EE) - single device used for a full year, unlike the monthly NuvaRing
5. Extended IUD use - 52 mg LNG-IUD (Mirena) approved for 8 years (up from 5); copper IUD duration also extended
6. Updated eligibility criteria (US MEC 2024, UKMEC 2025) - revised DMPA VTE risk classifications, new estrogen formulation categories
7. Perimenopause-specific counseling - shift toward natural estrogens (E4, estradiol valerate) after age 40