Agnusides are iridoid glycosides found predominantly in Vitex agnus-castus, also known as chasteberry. The use of Vitex agnus-castus for supporting the progesterone system and female reproductive health is well documented in both traditional herbal medicine and scientific research. The primary mechanism is believed to be the modulation of the hypothalamic-pituitary axis, leading to an increase in luteinizing hormone (LH) and a subsequent rise in progesterone production during the luteal phase of the menstrual cycle. Several clinical trials and reviews have reported the effectiveness of Vitex extracts in alleviating symptoms of premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), and certain types of menstrual irregularities, conditions often associated with relative progesterone deficiency.

The evidence is not specific to agnusides alone but to the whole extract, where agnusides are considered key active compounds. Systematic reviews (e.g., Cochrane Database Syst Rev, 2017) indicate moderate-quality evidence supporting Vitex's role in improving PMS symptoms, likely through dopaminergic effects that indirectly enhance progesterone secretion. However, direct, high-quality randomized controlled trials isolating agnusides are lacking, and most available studies use whole herb extracts. Overall, while there is a scientific rationale and moderate clinical evidence for using Vitex agnus-castus (and thus agnusides) to support progesterone-related body systems, the evidence is not robust enough for the highest rating.