Coordinación

Agnuside is a primary iridoid glycoside constituent of Vitex Agnus-Castus identified in both leaf and fruit extracts. It has been studied as one of the bioactive markers of Vitex, contributing to the herb's dopaminergic activity at pituitary D2 receptors and its prolactin-reducing effects that indirectly normalize luteal-phase progesterone synthesis. Agnuside is used as a standardization marker for Vitex extracts in clinical studies on progesterone balance and PMS.

Ashwagandha (Withania somnifera) is an Ayurvedic adaptogen whose withanolides modulate the hypothalamic-pituitary-adrenal (HPA) axis, reducing cortisol. Since chronic cortisol elevation suppresses GnRH and downstream LH/FSH, cortisol reduction can restore the ovulatory signaling needed for progesterone production. A 2025 randomized double-blind placebo-controlled trial in 60 perimenopausal women (300 mg extract twice daily, 56 days) showed significant increases in serum progesterone and estradiol and reductions in FSH and LH versus placebo (p<0.001). Evidence is strongest for stress-mediated hormonal disruption.

Raising luteal-phase progesterone is one of the most robustly documented pharmacological effects of Vitex in clinical trials. By suppressing excess prolactin via dopamine D2 agonism, VAC restores normal corpus luteum function, increasing progesterone secretion in the luteal phase. This has been confirmed in multiple RCTs including in hyperprolactinemia and luteal phase defect populations.

DHEA (dehydroepiandrosterone) is an adrenal steroid hormone that serves as a precursor in the steroidogenesis pathway and can be peripherally converted to progesterone, estrogen, and testosterone. DHEA supplementation is used to support hormonal balance including progesterone, particularly in women with adrenal insufficiency or age-related DHEA decline. Clinical evidence shows DHEA can modulate the steroid hormone milieu, and it is biochemically positioned upstream of progesterone production.

DIM (3,3'-diindolylmethane) is a phytonutrient formed from cruciferous vegetables that modulates estrogen metabolism, shifting breakdown toward less potent 2-hydroxy estrogen metabolites and away from more potent 16α-hydroxyestrone. By reducing the estrogen burden relative to progesterone, DIM indirectly supports progesterone balance in conditions of estrogen dominance. A 2024 retrospective cohort study (PMC, N=909 DIM users vs. 18,385 non-users) confirmed DIM significantly alters urinary estrogen metabolite profiles in premenopausal women. Clinical use includes 200 mg/day as part of estrogen-dominance and progesterone-support protocols.

Maca (Lepidium peruvianum/meyenii) is a Peruvian adaptogenic root used for centuries to support reproductive health and hormone balance. Unlike direct phytoestrogens, Maca works through the hypothalamic-pituitary axis to support overall endocrine function, potentially benefiting progesterone balance indirectly. A PMC-published biochemical and pharmacodynamic study found Maca promotes optimal hypothalamic-pituitary functioning, thereby improving functioning of all endocrine glands including those governing progesterone. Evidence for direct progesterone elevation is preliminary.

Magnesium is an essential mineral involved in multiple enzymatic reactions relevant to hormone synthesis and HPA axis regulation. It supports progesterone production by reducing cortisol (which competes for pregnenolone as a precursor), supporting LH pulsatility, and facilitating the enzymatic conversion of cholesterol to pregnenolone. Magnesium deficiency is associated with PMS and luteal phase symptoms, and supplementation is an evidence-based treatment for PMS. Typical dose for hormonal support is 300–400 mg/day as magnesium glycinate.

Pregnenolone is an endogenous steroid hormone biosynthesized from cholesterol in the adrenal glands, gonads, and brain. It is the direct biochemical precursor to progesterone, DHEA, cortisol, estrogen, and testosterone — the so-called 'mother hormone.' Supplemental pregnenolone is used to support progesterone balance by providing the upstream steroidogenic substrate. Because progesterone is synthesized directly from pregnenolone via 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase, pregnenolone availability is a rate-limiting factor in progesterone production, particularly under chronic stress when precursors are diverted toward cortisol.

Progesterone (listed as an ingredient in the candidate list) is the bioidentical hormone itself, used directly in supplemental form to address progesterone deficiency. It is pharmaceutically produced from plant sterol precursors (primarily diosgenin from wild yam or stigmasterol from soy) in laboratories. Clinically, oral micronized progesterone and transdermal progesterone creams are evidence-based treatments for luteal phase defect, PMS, perimenopause, and HRT. The evidence base for exogenous progesterone in hormonal balance is foundational in reproductive endocrinology.

Stigmasterol is the primary industrial precursor for the semisynthetic manufacture of progesterone. Its structural similarity to steroid hormones enables its conversion to progesterone in pharmaceutical synthesis. This is a well-documented biochemical and industrial relationship, not a direct supplemental claim.

Vitamin B6 (pyridoxine) plays a co-enzymatic role in steroid hormone synthesis and metabolism. It has been shown to support progesterone production by facilitating corpus luteum function and by reducing elevated prolactin, which when high suppresses ovulation and luteal progesterone synthesis. A double-blind clinical meta-analysis found 100 mg/day of B6 reduced PMS symptoms linked to low progesterone. At doses of 200–800 mg/day it has been reported to reduce blood estrogen and increase progesterone in clinical studies.

Vitamin C (ascorbic acid) is concentrated in follicular fluid and corpus luteum tissue and plays a direct role in luteal progesterone biosynthesis. A controlled clinical trial in 150 women with luteal phase defects found that 750 mg/day vitamin C significantly elevated serum progesterone (from ~7.5 to ~13.3 ng/mL vs. ~7.9 to ~8.7 ng/mL in controls) and improved pregnancy rates (25% vs. 11%). Vitamin C supplementation caused improvement in 53% of luteal phase defect cases in that study.

Vitex Agnus-Castus (chasteberry) is the most clinically documented herb for progesterone balance. It acts as a dopamine D2 agonist at the pituitary, reducing prolactin and indirectly normalizing luteal-phase progesterone synthesis. A randomized double-blind placebo-controlled trial in 52 women with luteal phase defects due to latent hyperprolactinemia showed significant reduction in prolactin, normalization of shortened luteal phases, and elimination of deficits in progesterone synthesis after 3 months at 20 mg/day. A systematic review of 12 RCTs confirmed superiority over placebo for PMS in 7 of 8 trials and found Vitex comparable to bromocriptine for reducing prolactin and improving mid-luteal progesterone.

Diosgenin from wild yam is chemically converted to progesterone in the laboratory and was historically the raw material for the first synthetic progesterone and oral contraceptives. Despite this industrial connection, the human body cannot perform this conversion, and clinical studies confirm that wild yam supplementation does not raise serum or salivary progesterone levels. The scientific evidence clearly separates industrial utility from in-vivo hormonal activity.

Zinc is required for LH synthesis in the pituitary and for progesterone production in corpus luteum granulosa cells. Zinc deficiency has been associated with luteal phase defects and anovulation. It also plays a role in regulating the estrogen-to-progesterone ratio. Clinical evidence and mechanistic studies establish zinc as a cofactor necessary for folliculogenesis, ovulation, and luteal steroidogenesis. Supplementation at 15–25 mg/day is used clinically to support progesterone production.