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When mast cells are activated in response to progesterone, the resulting histamine surge helps explain many of the hallmark features of APD, including: Hives (urticaria) caused by histamine-induced blood vessel dilation Intense itching (pruritus) driven by histamine signaling in the skin Angioedema , or deeper swelling beneath the skin and mucous membranes Asthma-like symptoms or shortness of breath , due to histamines effects on airway smooth muscle This mast cellhistamine connection also clarifies why treatments that target allergic pathways are often effective in APD, even though progesterone is a hormone rather than a classic allergen