Newer Contraceptives in Gynaecology

Study Notes - Berek & Novak's Gynecology + Recent Updates (2024-2025)

OVERVIEW - Key Principle

ALL hormonal contraceptives, even those containing estrogen, are progestin-dominant. The progestin performs the real contraceptive work via ovulation suppression or cervical mucus thickening. Estrogen assists with cycle control and adds to ovarian suppression, but progestin dominates.

• Berek & Novak's Gynecology, p. 730

1. NEWER ORAL CONTRACEPTIVE PILLS (OCPs)

A. Estetrol (E4) + Drospirenone (DRSP) - FDA Approved (2023)

• Selectively activates nuclear estrogen receptor alpha (ERα); does NOT activate membrane ERα
• Tissue-selective - different effects compared to ethinyl estradiol (EE) across liver, vascular endothelium, breast, brain
• Minimal interaction with hepatic cytochrome P450 enzyme system = fewer drug-drug interactions
• Lower impact on hemostatic and metabolic parameters than EE

• Ethinyl estradiol (EE) - the standard estrogen in old OCPs - has significant hepatic first-pass effects, increases VTE risk, and causes drug interactions
• E4 has negligible impact on liver, breast, and vascular endothelium due to its distinct tissue selectivity
• May reduce risk of venous thromboembolism (VTE) - awaiting confirmatory evidence

• Nelson AL, Expert Opin Pharmacother, 2023 | Battipaglia C, Minerva Obstet Gynecol, 2024

B. Drospirenone-Only POP (Progestin-Only Pill)

• Brand: Slynd (FDA approved 2019, gained wider adoption by 2023-24)
• Dose: Drospirenone 4 mg daily (24 active + 4 inactive tabs)
• Key difference from older POPs: Has a 24-hour extended window for missed pills (versus 3 hours for traditional norethindrone POPs)
• More forgiving for patients who sometimes miss pill timing
• Added to U.S. MEC 2024 - recommendations match norethindrone/norgestrel POPs except for patients with CKD (chronic kidney disease)
• Drospirenone has antimineralocorticoid and antiandrogenic properties

C. Extended-Cycle and Continuous-Cycle COCs

• Extended cycle: Active pills taken for 3 months at a time (e.g., Seasonale, Seasonique)
• Continuous cycle: Active pills taken indefinitely (e.g., Amethyst)
• Users experience more unscheduled spotting initially, but become amenorrheic over time
• Fewer cycle-triggered symptoms: headache, dysmenorrhea, pelvic pain
• Preferred for: Chronic pelvic pain, endometriosis, and women who prefer amenorrhea

D. 24/4 Dosing Regimen vs. Traditional 21/7

• 24 active + 4 placebo tablets vs. 21 active + 7 placebo
• Shorter hormone-free interval = better ovulation suppression; ovarian follicles mature more during the 7-day than the 4-day interval
• Examples: Yaz (20 μg EE + drospirenone), Lo Loestrin Fe

2. TRANSDERMAL PATCH

• Worn for 1 week, changed weekly for 3 consecutive weeks, followed by 1 patch-free week
• Constant low serum EE levels (less peak-and-trough variation than pills)
• Compliance advantage: Perfect use in 88.2% of patch cycles vs. 77.7% of pill cycles (p < 0.001)
• Berek & Novak's Gynecology, p. 749

3. VAGINAL RING

NuvaRing (Classic)

• Size: 54 mm outer diameter, 4 mm cross-section; soft, flexible ring
• Hormones: Etonogestrel 120 μg/day + EE 15 μg/day - lowest estrogen combination method
• Worn for 3 weeks, removed for 1 week; can be removed for intercourse (must replace within 3 hours)
• EE blood levels ~1/3 of those from a standard COC; etonogestrel ~40% of equivalent COC - yet ovulation fully suppressed
• Pearl Index: 1.18 (95% CI 0.73-1.80)
• Fewer days of irregular bleeding than comparable COC
• Berek & Novak's Gynecology, p. 749

Annovera (Newer - FDA 2018, growing use)

• Segesterone acetate 150 mg + EE 17.4 mg in a single ring
• Used for 13 cycles (1 full year) - worn 21 days in, 7 days out each cycle, same ring reused
• Major advance: one ring for the entire year instead of monthly replacement
• Convenient for women with irregular pharmacy access

4. INTRAUTERINE DEVICES (IUDs)

Currently available in USA (Berek & Novak, p. 721):

• "Biologic foam" - fibrin, phagocytic cells, proteolytic enzymes alter intrauterine environment
• Stimulate prostaglandins - smooth muscle contraction + inflammatory response
• Copper IUDs: continuous copper release = greater inflammatory response, sperm are immobilized
• LNG-IUDs: profound endometrial effect; cervical mucus thickening; some ovulation suppression

• Immediate postpartum IUD placement recommendations were revised
• Increased safety data supports placement within 10 minutes after placental delivery

5. SUBDERMAL IMPLANTS

Nexplanon (Etonogestrel implant) - Gold Standard

• Single 4 cm x 2 mm rod inserted subdermally in upper arm
• Releases etonogestrel (active metabolite of desogestrel)
• Duration: 3 years (studies confirm efficacy up to 5 years)
• Most effective reversible contraceptive - lowest failure rate of any hormonal method
• Mechanism: primarily ovulation suppression (etonogestrel is more potent than levonorgestrel)
• In first year: ovulation inhibited almost completely; by year 4, 41% cycles may be ovulatory
• Hematological safety: No increase in thrombosis risk; no published cases linking etonogestrel implant to VTE or MI
• Progestin-only = safe in women with migraine with aura, smoking >35 years, history of VTE
• Berek & Novak's Gynecology, p. 733

6. INJECTABLES

DMPA (Depo-Provera) - Established Injectable

• Depot medroxyprogesterone acetate 150 mg IM every 13 weeks
• OR DMPA-SC (subcutaneous) 104 mg - patient can self-administer
• U.S. SPR 2021/2024 update: Confirmed self-administration of DMPA-SC as safe and effective
• Return of fertility delayed: 10-12 months on average after last injection (can be up to 18-22 months)

• Progestogen-only injectables can now be safely offered immediately after childbirth (previously, there was a 6-week wait recommendation to avoid impact on neonatal health and lactation)

7. EMERGENCY CONTRACEPTION (EC)

• LNG works ONLY before ovulation - it is NOT an abortifacient
• Copper IUD: 100% efficacy up to 5 days post-coitus; 94% of patients continue using it at 12 months (cost-effective, doubles as long-term contraception)
• Ulipristal acetate: SPRM - can work even in the late follicular phase when LNG is ineffective (if ovulation is imminent)
• WHO MEC 2025 Update: Emergency contraception can be repeated within the same cycle (previously discouraged)
• Berek & Novak's Gynecology, p. 758-760

8. NON-HORMONAL NEWER METHODS

Phexxi (Vaginal pH Modulator) - FDA 2020

• Lactic acid + citric acid + potassium bitartrate gel
• Lowers vaginal pH to 3.5 or below; sperm require pH 7-8 to survive/motilize
• Applied vaginally before each act of intercourse (within 1 hour)
• Typical use Pearl Index: ~27.5 pregnancies/100 women-years (lower than condoms alone)
• No hormones - safe for women who cannot use hormonal methods
• Added to U.S. MEC 2024 as a new barrier/vaginal method category

9. MALE CONTRACEPTIVES (Newer Research)

Hormonal Male Contraception

• Mechanism: Same negative feedback of sex steroids that suppresses ovulation can suppress spermatogenesis
• Testosterone undecanoate (TU) monthly injections: effective in Asian men (near-universal azoospermia); only ~86% efficacy in Caucasian men
• TU + progestin combination (e.g., etonogestrel implant + TU injections): Only 3% failure to suppress sperm to <1x10⁶/mL in Caucasian men
• Nesterone (progestin) + Testosterone gel (transdermal): 89% suppression of sperm to ≤1x10⁶/mL with minimal side effects - currently in Phase 3 trial
• Side effects: acne, night sweats, libido changes (usually increased), weight gain

Non-Hormonal Male Contraception (Experimental)

• Berek & Novak's Gynecology, p. 760

10. LACTATION AMENORRHEA METHOD (LAM)

• Effective when: exclusively breastfeeding + amenorrhea + <6 months postpartum (all three criteria)
• Failure rate: ~2% if all criteria met; rises quickly if any criteria not met
• Progestogen-only injectables: WHO MEC 2025 now permits immediate postpartum use without waiting 6 weeks

SUMMARY TABLE: Efficacy of Newer Contraceptives

IMPORTANT RECENT UPDATES (2024-2025)

U.S. MEC 2024 (CDC, August 2024)

1. New methods added: E4/DRSP COC, drospirenone POP, Phexxi (vaginal pH modulator), Annovera (annual ring)
2. New condition: Chronic Kidney Disease (CKD) - recommendations added for nephrotic syndrome, hemodialysis, peritoneal dialysis
3. Revised recommendations for: sickle cell disease, anticoagulant therapy, cirrhosis, liver tumors, solid organ transplantation, IUD placement postpartum
4. Sickle cell disease: Increased safety concern for combined hormonal contraception and DMPA
5. Progestin-only + liver disease: Decreased safety concern (progestin-only methods now safer in more liver disease scenarios)
6. DMPA-SC self-administration formally endorsed

WHO MEC 6th Edition (November 2025)

1. Progestogen-only injectables can be offered immediately after childbirth (no longer need to wait)
2. Emergency contraception can be repeated within the same menstrual cycle
3. Hormonal methods can be safely used by women taking PrEP (HIV pre-exposure prophylaxis)
4. Updated evidence reviewed with formal GRADE methodology

HIGH-YIELD POINTS FOR EXAMS

1. Estetrol = first new estrogen in OCP since 1960; produced by fetal liver; lower VTE risk; combined with drospirenone as Nextstellis
2. Annovera = annual vaginal ring (segesterone + EE); single ring for 13 cycles
3. Phexxi = non-hormonal vaginal gel; lowers pH; ideal for women who cannot use hormones
4. Drospirenone POP (Slynd) = 24-hour missed pill window; antimineralocorticoid; also for PMDD
5. Copper IUD = most effective EC; 100% efficacy within 5 days; offers ongoing long-term contraception
6. Etonogestrel implant = single most effective reversible contraceptive; no VTE risk; safe in migraine with aura
7. Emergency contraception can now be repeated in the same cycle (WHO MEC 2025 update)
8. Progestogen-only injectables can now be given immediately postpartum (WHO MEC 2025)
9. Vasalgel/RISUG = experimental male non-hormonal methods; reversible vas deferens occlusion
10. U.S. MEC 2024 is the current CDC standard; replaced the 2016 edition in August 2024

• Berek & Novak's Gynecology, 16th Ed. - Chapter 14: Contraception (pp. 721-762)
• Nelson AL. Drospirenone and estetrol. Expert Opin Pharmacother. 2023 (PMID: 37691580)
• Battipaglia C, et al. Insights on estetrol. Minerva Obstet Gynecol. 2024 (PMID: 39283289)
• Barton BE, et al. Reversible female contraceptives. Biol Reprod. 2024 (PMID: 37941453)
• U.S. MEC 2024 Update - PMC (CDC, August 2024)
• WHO MEC 6th Edition + SPR, November 2025

Note: While Williams Gynecology is referenced in your request, the institutional library contains Berek & Novak's Gynecology which is an equally authoritative standard gynecology textbook covering this topic comprehensively. The content has been cross-referenced with the most current CDC (U.S. MEC 2024) and WHO (MEC 6th Ed., 2025) guidelines.