Clinical Features

Possible mechanisms
Autoimmune progesterone dermatitis

Autoimmune progesterone anaphylaxis
  • Luteal phase of menstrual cycle
  • Starts 3-10 days before onset of menses and regresses/resolves at or shortly after (1-2 days) the onset of menstruation
  • Cyclic monthly episodes of urticaria most common; erythema multiforme, folliculitis, purpura, stomatitis, eczema, angioedema, papulovesicular eruptions, fixed drug eruptions, and vulvovaginal pruritis have also been reported

  • May also include other systems (airway angioedema, dyspnea, GI) and meet criteria for anaphylaxis
  • IgE-mediated, cell-mediated, and/or direct mast cell degranulation triggered by progesterone has been hypothesized
  • Detection of anti-progesterone IgG in some cases suggests an autoimmune basis
  • Most have previous exposure to exogenous progesterone
Catamenial anaphylaxis
  • Develops during menstruation
  • Similar to above
  • Endometrial-derived mediators such as PGF2-alpha or PGI2 (prostacyclin) may leak into the blood stream during menstruation
  • Similar syndromes have been reported (less frequently) suggesting estrogen sensitivity

Menstrual Cycle

Menstrual cycle 2.jpg


  • Rare; other possible etiologies should be fully considered, e.g. NSAID allergy
  • Proposed diagnostic criteria
    1. Skin lesions related to the menstrual cycle
    2. Positive response to intradermal testing with progesterone
      • Note that skin testing may not be positive in otherwise convincing cases
    3. Symptomatic improvement after inhibiting progesterone secretion by suppressing ovulation

Skin Testing

  • Progesterone skin testing
    • Progesterone in sesame oil (50 mg/mL) with 10% benzyl alcohol for IM injection is easily available
      • Sesame proteins, benzyl alcohol, and oil may cause allergic or irritant reactions (acute and/or delayed onset)
      • Sesame oil with 10% benzyl alcohol may be obtained from compounding pharmacies for use as a negative control; healthy family member or staff may also serve as additional control
      • Progesterone aqueous solution not easily available but can be ordered from compounding pharmacy
    • Protocol (Castells)
      • SPT with progesterone 50 mg/mL (1:1)
      • ID with 1:10,000 (0.005 mg/mL), 1:1000 (0.05 mg/mL), 1:100 (0.5 mg/mL), and 1:10 (0.5 mg/mL) dilutions in normal saline
        • Use of full strength (1:1) ID skin testing has been reported by others
      • Ask patients to report/photograph delayed reactions
  • Skin testing with medroxyprogesterone also reported


  • Acute symptomatic treatment for hypersensitivity reactions includes H1/H2 antihistamines, systemic steroids, epinephrine
    • Tends to be poorly respsonsive to antihistamines/steroids
    • Topical steroids reported to be effective for cutaneous lesions in some cases
    • Epinephrine auto-injector should be carried by patient if there is a history of anaphylaxis-like symptoms
  • Avoid exogenous progesterone
  • Endogenous progesterone suppression
    • Conjugated estrogens (e.g. Premarin)
    • GnRH/LH-RH agonists (e.g. leuprolide, triptorelin)
    • Danazol, stanazolol
    • Tamoxifen
    • Hysterectomy/oophorectomy is definitive treatment
  • Progesterone desensitization
    • Oral, vaginal suppository, and IM desensitization protocols have been reported
  • In a few cases, may resolve on its own without treatment, or resolve during pregnancy

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Progesterone in Oil Injection - package insert