Sir,In view of an excellent article published in your esteemed journal aiming to investigate the efficacy of progesterone supplementation in patients with unexplained recurrent miscarriages,[1] we would like to add some vital information related to the progesterone and its action on the oral cavity, and it is clear that endogenous sex steroid hormones play a significant role in modulating the periodontal tissue responses. A hormone critical for females is progesterone secreted by the corpus luteum, placenta, and the adrenal cortex, and it is active in bone metabolism and has a significant effect in the coupling of bone resorption and bone formation by engaging osteoblast receptors directly.[2] Progesterone has significant biological actions that can affect other organ systems including the oral cavity. Receptors for progesterone have been demonstrated in the gingiva in which the gingiva can be thought of as a target organ for progesterone. Progesterone receptors are also found on periosteal fibroblasts, scattered fibroblasts of the lamina propria, and also periodontal ligament fibroblasts and osteoblasts.[3] Progesterone increases proliferation, dilatation, tortuosity, and permeability of gingival micro-vasculatures, facilitates bone resorption, decreases collagen production; thus, promoting tissue catabolism and delaying repair. Progesterone increases vascular dilatation; thus, increases permeability; Increases prostaglandin E2 in the gingival crevicular fluid; Reduces glucocorticoid anti-inflammatory effect; Inhibits collagen and non-collagen synthesis in periodontal ligament fibroblasts; Inhibits proliferation of the human gingival fibroblast proliferation and alters rate and pattern of collagen production in gingiva resulting in reduced repair and maintenance capability, thereby leading to periodontal disease and destruction.[4] All these factors related to an oral cavity (Periodontium) have to be kept in mind while progesterone supplementation is required as part of the treatment plan. A multidisciplinary approach between the reproductive medicine and oral medicine would be better for such progesterone supplementations.