What are the risks and alternatives to using Gestanol (progesterone) vaginal suppositories?

Gestanol (Progesterone) Vaginal Suppositories: Risks and Alternatives

Primary Risks

The most critical risk of progesterone vaginal suppositories is severe allergic reaction in patients with peanut allergies, as many micronized progesterone formulations contain peanut oil as an excipient and can trigger anaphylaxis. 1

Allergy-Related Risks

• Individuals with severe peanut allergies should never receive micronized progesterone capsules or suppositories containing peanut oil due to anaphylaxis risk 1
• Clinicians must specifically inquire about peanut allergies before prescribing any progesterone formulation 1
• The suppository base itself affects progesterone absorption, with polyethylene glycol bases showing highest bioavailability compared to cocoa butter or glycerinated gelatin 2

Contraindications

• Hormone receptor-positive breast cancer is an absolute contraindication to progesterone therapy 1
• Combined estrogen-progesterone therapy increases breast cancer risk (RR 1.24), particularly in women with prior hormone therapy use (RR 1.86) 3
• Endometrial cancer risk increases with unopposed estrogen, though adding progesterone reduces this risk 3
• Ovarian cancer risk may increase with prolonged estrogen-progesterone use (≥5 years) 3

Other Significant Risks

• Probable dementia risk increases in postmenopausal women ≥65 years (RR 2.05) when using combined estrogen-progesterone therapy 3
• Retinal vascular thrombosis can occur; discontinue immediately if sudden vision loss, diplopia, or papilledema develops 3
• Bleeding irregularities are common but generally not harmful 4

Clinical Indications and Alternatives

For Preterm Birth Prevention

In women with singleton pregnancies and short cervical length (≤20 mm at 18-24 weeks), vaginal progesterone (90 mg gel or 200 mg suppository) significantly reduces preterm birth and improves neonatal outcomes. 4

Evidence-Based Recommendations:

• Vaginal progesterone reduces preterm birth <33 weeks by 45% (RR 0.55) in women with short cervix 5
• Also decreases respiratory distress syndrome (RR 0.39), neonatal morbidity/mortality (RR 0.57), and birth weight <1500g (RR 0.47) 5
• Updated meta-analysis confirms reduction in preterm birth ≤34 weeks (RR 0.66) without adverse neurodevelopmental effects at 2 years 6

Alternative for Peanut Allergy:

• Vaginal progesterone gel formulations do not contain peanut oil and are the safe alternative for patients with peanut allergies 1

When NOT to Use:

• Insufficient evidence for progesterone in multiple gestations, preterm labor, or preterm premature rupture of membranes (PPROM) 4
• For women with prior spontaneous preterm birth, 17-hydroxyprogesterone caproate (17P) 250 mg IM weekly is preferred over vaginal progesterone 4

For Endometrial Protection in Hormone Therapy

Oral micronized progesterone is recommended as first-choice progestogen for opposing estrogen therapy in postmenopausal women with intact uterus. 7

Advantages Over Synthetic Progestins:

• Natural progesterone minimizes or eliminates metabolic and vascular side effects seen with synthetic progestins (norethisterone, medroxyprogesterone acetate) 7
• Does not suppress the vasodilating effects of estrogens 7
• Better cardiovascular profile and possibly lower breast cancer risk compared to synthetic progestins 8

Dosing Options:

• 300 mg daily at bedtime for 10 days/month (for regular bleeding) 7
• 200 mg for 14 days/month 7
• 100 mg for 25 days/month (for amenorrhea) 7
• Only side effect is mild, transient drowsiness, minimized by bedtime dosing 7

For Luteal Phase Support

Progesterone vaginal suppositories provide effective luteal phase support in assisted reproductive technology and treat luteal phase deficiency causing infertility. 8

Key Clinical Pitfalls

• Always screen for peanut allergies before prescribing—this is non-negotiable 1
• Do not use progesterone for universal preterm birth prevention without documented short cervix 4
• Avoid in multiple gestations for preterm birth prevention (no proven benefit) 4
• Monitor for vision changes and discontinue immediately if retinal symptoms occur 3
• In women ≥65 years, weigh dementia risk carefully before initiating hormone therapy 3

Alternative Contraceptive Context

The provided evidence primarily addresses injectable contraceptives (DMPA) rather than progesterone suppositories for contraception 4. For contraceptive purposes, progestin-only pills or other methods would be more appropriate than vaginal progesterone suppositories, which are not standard contraceptive agents.