on August 03, 2026
Climacteric represents an endocrine transition phase characterized by the progressive decline in ovarian activity and estrogen secretion. This hormonal readjustment induces clinical manifestations that significantly impact quality of life, including vasomotor symptoms (hot flashes, night sweats), neuropsychiatric disorders (anxiety, low mood, insomnia), atrophic changes in the genitourinary area, and alterations in the metabolic and bone profile. Dietary supplementation and rational phytotherapy aim to modulate these symptom complexes through active principles with specific biological activities at both central and peripheral levels.
Neuroendocrine modulators and central-acting phytotherapeutics
The regulation of neurotransmitters and the hypothalamus-pituitary axis constitutes a priority target in the management of mood, sleep, and appetite control alterations.
· Chaste tree (Vitex agnus-castus): Acts on the central dopaminergic system (particularly on D2 receptors), exerting a modulating action on prolactin secretion and indirectly influencing endogenous opioid circuits. Recent evidence indicates that chaste tree extract contributes to the stimulation of endogenous melatonin synthesis, promoting the restoration of circadian rhythms, improvement of sleep architecture, and containment of compensatory appetite peaks associated with anxious-depressive states.
· Hops (Humulus lupulus): Rich in prenylflavonoids (including 8-prenilnaringenin, one of the most potent phytoestrogens isolated in nature), it combines phytoestrogenic activity with marked sedative and antispasmodic properties. The sedative action is attributable to the bitter components (humulone and lupulone) and their degradation derivatives, which act on the GABAergic system, reducing hyperexcitability and sleep onset latency. Caution is required when using it in patients with a history of hormone-sensitive neoplasms (e.g., estrogen-dependent breast cancer) or in combination with psychotropic drugs and alcohol due to the enhancement of depressive effects on the central nervous system.
· Rhodiola rosea: A primary adaptogen, standardized to rosavin and salidroside. At the central level, it inhibits monoamine oxidase (MAO-A and MAO-B) and catechol-O-methyltransferase (COMT), increasing the synaptic availability of serotonin (5-HT), dopamine, and noradrenaline. This mechanism reduces the craving for high-glycemic-index carbohydrates and improves tolerance to psycho-physical stress. At the peripheral level, rosavin stimulates hormone-sensitive lipase (HSL) in adipocytes, promoting lipolysis and the reduction of visceral adipose tissue when combined with regular physical activity.
· Griffonia simplicifolia: Natural source of 5-hydroxytryptophan (5-HTP), a direct precursor of serotonin. Unlike L-tryptophan, 5-HTP freely crosses the blood-brain barrier without competing for amino acid transporters and does not require the hydroxylation enzymatic phase (the rate-limiting step of synthesis). Its rapid effect on serotonergic levels makes it suitable for acute phases of mood decline; however, to avoid habituation or receptor downregulation, temporary use or alternation with molecules with more gradual modulation, such as Rhodiola rosea, is recommended.
Plant steroidal extracts and bone and mucosal tissue health
· Dioscorea villosa (Wild Yam): Its phytocomplex is characterized by high concentrations of diosgenin, a steroidal saponin. Although the direct enzymatic conversion of diosgenin into dehydroepiandrosterone (DHEA) occurs mainly in vitro and in chemical synthesis contexts, the standardized dry extract (e.g., 20% diosgenin at doses of 400 mg/day) clinically demonstrates attenuation of vasomotor symptoms, improvement in vaginal epithelial hydration (reducing dyspareunia), and an action protecting bone tissue, limiting the loss of bone mineral density (BMD) induced by hypoestrogenism.
Hormones and essential micronutrients
· Melatonin: Hormone produced by the pineal gland, whose plasma levels undergo a physiological reduction with advancing age. Its administration reduces sleep onset latency and mitigates night awakenings secondary to hot flashes. It also plays a key role in modulating osteoblastic and osteoclastic activity, promoting bone remodeling. In accordance with regulatory provisions (EU Regulation 432/2012 and Ministry of Health indications), the allowed dosage in food supplements is 1 mg/day for sleep induction and 0.5 mg for jet lag management.
· Vitamin D (Cholecalciferol): Pro-hormonal substance essential for calcium and phosphate homeostasis. In addition to the prevention of osteopenia and osteoporosis, vitamin D expresses receptors (VDR) in multiple tissues, influencing the immune response, carbohydrate metabolism, and cardiovascular protection. The dosage must be personalized based on 25(OH)D blood levels; ministerial guidelines indicate a daily dietary and supplemental intake between 400 and 800 IU, with adequate sun exposure.
· B Vitamins (B1 and B6): Vitamin B1 (Thiamine, supplement limit: 25 mg/day) acts as a cofactor in carbohydrate metabolism, optimizing glucose utilization in insulin-resistant subjects. Vitamin B6 (Pyridoxine, limit: 9.5 mg/day) operates as an indispensable cofactor for pyridoxal-phosphate-dependent decarboxylase, an enzyme that converts 5-HTP into serotonin, supporting protein synthesis and countering sarcopenia.
· Vitamin C (Ascorbic Acid): Water-soluble antioxidant essential for the hydroxylation of proline and lysine in collagen synthesis. It is decisive in countering mucosal atrophy and the resorption of cutaneous connective tissue. Given the saturation of renal transporters and the reabsorption threshold at approximately 250 mg, the administration of the maximum allowed dosage (1000 mg/day) benefits from division into multiple daily doses to minimize the urinary excretion of the surplus.
· Magnesium: Intracellular cation involved in over 300 enzymatic reactions. Its deficiency is correlated with irritability, anxiety, asthenia, and increased insulin resistance. The choice of salt form must correspond to the clinical condition:
o Magnesium pidolate: Neurostimulant action (not recommended in the presence of insomnia or marked anxiety).
o Magnesium sulfate: Endowed with an intestinal osmotic effect (useful in constipation, less indicated with regular bowel movements).
o Magnesium citrate: Promotes urinary alkalinization, preventing lithiasis from hydroxyapatite stones.
· Alpha-Lipoic Acid (Thioctic Acid): Amphipathic molecule (hydro- and liposoluble) capable of regenerating other endogenous antioxidants such as glutathione (GSH), vitamin C, and vitamin E. Acts as a cofactor in the oxidative decarboxylation of pyruvate, improving insulin sensitivity, glycemic control, and countering oxidative stress associated with bone mass loss. Working dosages vary between 50 mg and 800 mg/day based on the body mass index (BMI) and the patient's metabolic profile.
Vascular, sedative, and antioxidant support
· Hawthorn (Crataegus monogyna): Rich in hyperoside and vitexin, it exerts a positive inotropic and negative chronotropic action, associated with a hypotensive and sedative effect on the autonomic nervous system (particularly useful in sympathotonic subjects with cardiac erethism secondary to hot flashes).
· Passionflower: Contains flavonoids (vitexin, isovitexin) with a modulating action on the GABA-A receptor. Reduces sleep fragmentation and nighttime restlessness.
· Grape seeds (Vitis vinifera): Concentrated in oligomeric proanthocyanidins (OPC), bioflavonoids with high antioxidant potency. Clinical studies show that the administration of grape seed extracts (100-200 mg/day) for 8 weeks reduces scores related to physical and psychological symptoms using validated scales (such as the Athens Insomnia Scale and Hospital Anxiety and Depression Scale), resulting in an improvement of blood pressure parameters and body composition.
Progesterone and tumor receptors: new research perspectives
In the context of breast oncology and hormone therapy, scientific evidence published in Nature has clarified the role of the progesterone receptor (PR) in estrogen receptor-positive (ER+) breast tumors. Historically, the presence of progestin steroid receptors has been associated with a more favorable prognosis. Researchers at the Cambridge Research Institute and the University of Adelaide have demonstrated that the activation of the PR receptor by progesterone alters the binding map of the estrogen receptor (ER-alpha) on DNA, reprogramming cellular gene expression. This receptor "crosstalk" slows the proliferation of tumor cells and increases their susceptibility to conventional anti-estrogen treatments (such as tamoxifen), opening therapeutic perspectives on the targeted use of progestins to optimize clinical prognosis.
Bibliographic References
1. Ngan, A., & Conduit, R. (2011). A double-blind, placebo-controlled investigation of the effects of Passiflora incarnata (Passionflower) herbal tea on subjective sleep quality. Phytotherapy Research, 25(8), 1153-1159.
2. Terauchi, M., et al. (2014). Effects of grape seed proanthocyanidin extract on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women: a randomized, double-blind, placebo-controlled study. Menopause, 21(10), 1089-1096.
3. Mohammed, H., et al. (2015). Progesterone receptor modulates ERα action in breast cancer. Nature, 523(7560), 313-317.
4. Rossi, R., et al. (2012). Rhodiola rosea for physical and mental fatigue: a systematic review of randomized controlled trials. BMC Complementary and Alternative Medicine, 12, 70.
5. Erenloyburgu, S., et al. (2018). Evaluating the efficacy of Vitex agnus-castus in sleep disorders and vasomotor symptoms in menopausal transition. Journal of Herbal Medicine, 14, 22-28.
6. Di Pierro, F., et al. (2015). Clinical evaluation of the administration of α-lipoic acid in postmenopausal women with metabolic syndrome. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 8, 435-441.
7. Ministero della Salute. (2012). Guidelines for the prevention of osteoporosis and nutritional intake of Vitamin D and Calcium. Notiziario Epidemiologico Nazionale.
8. EFSA Panel on Dietetic Products, Nutrition and Allergies. (2012). Scientific Opinion on the substantiation of health claims related to melatonin and reduction of latency to falling asleep pursuant to Regulation (EC) No 1924/2006. EFSA Journal, 10(2), 2580.
