Menopause is a natural biological phenomenon in women, typically occurring between the ages of 45 and 55 years (1). It is characterised by the persistent cessation of menstruation for at least 12 consecutive months, followed by a decline in ovarian follicles (2), which leads to decreased levels of estradiol, along with increased follicle-stimulating hormone (FSH), ultimately resulting in estrogen deficiency. Menopause is a natural physiological process, frequently accompanied by symptoms that can significantly impact a woman's quality of life (3). Previous studies have reported that approximately 60% of women with menopause experience mild symptoms, 20% of them report severe symptoms, and 20% remain asymptomatic. The common menopausal symptoms are hot flashes, excessive sweating, reduced libido, sleep disturbances, urogenital issues (vaginal dryness, painful intercourse, and recurrent bladder infections), breast tenderness, joint pain, cognitive changes, and mood disturbances, including depression and anxiety symptoms (4). The available treatments for these symptoms are hormone therapy (HT), prescription antidepressants, physical activity, and lifestyle modifications (5).

Ayurveda, the traditional system of medicine in India, has long utilized adaptogenic herbs to support female reproductive health and hormonal balance. Among these, Shatavari (Asparagus racemosus Willd.) and Ashwagandha (Withania somnifera L. Dunal) are the two most extensively used botanical therapies for hormone regulation and stress adaptation. Shatavari is a well-known herb in Ayurveda for its phytoestrogenic and rejuvenating properties. It is commonly known as Wild Asparagus or Indian Asparagus. It is referred to as the “Queen of Herbs”. It was traditionally said to foster attachment and affection. Shatavari is believed to exert its effects through phytoestrogenic activity of its steroidal saponins (Shatavarins), which have affinity for estrogen receptors and may modulate gonadotropin levels, in addition to antioxidant and anti-inflammatory actions (6). Shatavari acts as a primary rejuvenative herb for women, helps to regulate hormonal balance, improve reproductive health, and reduce menopausal symptoms such as hot flashes, insomnia, and mood disturbances. Additionally, it supports adrenal function and helps to maintain healthy estrogen levels during menopause to relieve menopausal symptoms such as hot flashes, insomnia, depression, and excessive sweating (7). Shatavari root extract contains various phytoconstituents, including Shatavarins, which are steroidal saponins in structure and have affinity towards estrogen receptors (8) and exhibit estrogen-like activity, which helps in regulating overall hormonal regulation. It offers more benefits, such as supporting heart health, a healthy mood, aiding digestion, and having antioxidant and anti-inflammatory effects (6).

Ashwagandha, another well-known, revered herb in Ayurveda, accompanies Shatavari with its adaptogenic properties. Ashwagandha acts primarily through modulation of the hypothalamic-pituitary-adrenal (HPA) axis, reducing cortisol levels and enhancing stress resilience, alongside potential neuromodulatory and reproductive health benefits. It includes withanolides, sitoindosides, flavonoids, and steroidal lactones (9). Ashwagandha has been extensively studied for its effects, such as helping the body adapt to stress, and its role in hormonal regulation (10). In healthy women, it is still an area that needs further research. When used in combination with Shatavari, the two herbs may offer additive benefits, particularly in promoting women's sexual well-being (11, 12). Ashwagandha also supports reproductive function, aids in promoting a healthy balance in sexual and reproductive health (13). Although both Shatavari and Ashwagandha have been traditionally used for supporting women's health, the scientific evidence on their role in managing menopausal symptoms remains limited, particularly regarding their combined use at the extract concentrations of Shatavarins (>10%) and Withanolides (>5%) (7, 10, 14).

This prospective, randomized, double-blind, three-arm, placebo-controlled study assessed and compared the efficacy and safety of Shatavari alone and Shatavari combined with Ashwagandha, in comparison to placebo.

A total of 135 participants were randomized to receive SHT (n = 45), ARE-SHT (n = 45), or PL (n = 45). During the study period, ten participants were lost to follow-up (Figure 1). As a result, 125 participants were included in the efficacy analysis (PP dataset), while 135 participants were analyzed for both safety and efficacy (ITT dataset). The primary reasons included withdrawal of consent due to personal reasons (n = 4), non-compliance with study visits or procedures (n = 3), and loss of contact despite repeated attempts (n = 3). No participant discontinued due to adverse events. The CONSORT flow chart is depicted in Figure 1.

Symptoms of perimenopause and post menopause can have a big impact on women's daily activities, productivity, and overall quality of life (20). Shatavari, a medicinal plant traditionally used in Ayurveda, contains phytoestrogenic compounds that have affinity for estradiol receptor-binding (21, 22). Along with the Shatavari root extract-alone arm, the Shatavari and Ashwagandha root extracts combination arm was included purely on an exploratory basis, with the intent to generate preliminary insights into potential additive effects. The study was not powered to draw definitive conclusions regarding the combination, and therefore, findings related to this arm should be considered hypothesis-generating. The primary objective of the study was to evaluate the efficacy of Shatavari root extract alone; however, the three-arm design also allowed for distinguishing the effects of Shatavari root extract alone and any additional benefits of the combination, thereby providing a more comprehensive clinical evaluation.

The study duration was set at 8 weeks, consistent with prior trials evaluating Ashwagandha and Shatavari in menopausal populations, which reported clinically meaningful improvements within a similar timeframe (12, 23). The dosing strategy was chosen to achieve a safe and balanced phytotherapeutic effect, avoiding excessive Ashwagandha exposure relative to Shatavari while ensuring clinical efficacy.

A study conducted by Gudise et al. (23), which was an eight-week, multicenter, interventional, prospective, randomized, double-blind, placebo-controlled trial on 70 females, reported a significant improvement in night sweats and hot flashes at follow-up visits on day 30 and day 60 (p < 0.0001). Though in the current study, hot flashes did not show significant improvement in week 4 but shown significance at week 8 between the groups. Despite this, it was observed that the somato-vegetative domain showed significant improvements in week 8 (p < 0.0001), as well as the psychosocial domain showed significant improvement in the SHT vs. PL (p < 0.0001) and ARE-SHT vs. PL (p < 0.0001) comparison. No significant change was observed between the ARE-SHT vs. SHT groups, suggesting that the combination is as effective as the SHT monotherapy. Gudise et al. (23), specifically focused on Shatavari monotherapy (500 mg/day), the current trial explored both Shatavari alone (300 mg/day) and a combination with Ashwagandha, thereby broadening the scope to include synergistic effects on mood and stress outcomes in addition to vasomotor symptoms.

A 12-week study conducted on 117 healthy women (aged 40–65 years), investigating a combination of Tinospora cordifolia (75 mg), Asparagus racemosus (100 mg), Withania somnifera (100 mg), and Commiphora mukul (225 mg) compared to a placebo (maltodextrin) was reported by Steels et al. (24). The results reported were significant improvements in the vasomotor (p < 0.001), psychosocial (p < 0.001), physical (p = 0.02), and sexual domains (p < 0.001) and in the overall MENQOL score. In contrast, the current study showed no significant improvements in the physical (p = 0.113), sexual domains (p = 0.238), or MENQOL total score (p = 0.117) between groups at week 8.

A 30-day trial by Leonard et al. (25) assessing the effect of ARE (225 mg/day) on cognitive function and mood reported, improvement in 60 participants demonstrating a significant difference in various POMS subdomains (p < 0.0001). In the current study, a significant baseline difference was observed in the POMS Confusion subscale between groups. To account for this imbalance, outcome analyses were adjusted for baseline Confusion scores along with other covariates (age, menopausal status, BMI, and FSH) using a generalized linear model. The intervention-related improvements in mood, stress (PSS), and emotional role functioning (ERA) remained consistent after adjustment, suggesting that the baseline difference in Confusion did not bias the overall results.

In the present study, ERA showed significant improvement at week 4 (p = 0.015) and week 8 (p = 0.025). Additionally, ARE-SHT vs. PL showed greater improvements compared to both SHT vs. PL and ARE-SHT vs. SHT, signifying an additive effect of ARE-SHT, which was comparable to or more effective than SHT alone.

A study conducted by Gopal et al. (12), on 100 women with climacteric symptoms demonstrated that ARE (300 mg BID) significantly reduced MENQOL scores (p < 0.0001), along with improvements in the somato-vegetative (p = 0.0152), psychological (p = 0.0003), and urogenital (p < 0.0001) domains. Gopal et al. (12) exclusively examined Ashwagandha at higher doses in perimenopausal women; the current trial tested a lower dose of Ashwagandha root extract (250 mg/day) in combination with Shatavari root extract and included a wider menopausal spectrum. This design allowed us to investigate not only single-agent but also combination effects, thereby providing novel insights into complementary phytotherapeutic approaches. The current study aligns with the study findings, a significant difference in PSS scores was observed in week 4 (p = 0.035) and week 8 (p < 0.0001). Post hoc analysis revealed a significant difference between ARE-SHT and SHT groups, suggesting combination therapy is more effective than monotherapy (12).

Based on the findings from both the previous and present studies indicated that ARE and SHT can work together to reduce the symptoms of stress, whereas the menopausal symptoms can be improved with either the combination or SHT alone. Mild adverse events were reported, including loose stools and dizziness in the ARE-SHT group, nausea in the SHT group, and headache in the PL group. However, these adverse events were mild, and the combination therapy was found to be safe and well (26, 27).

At week 8, participants in the ARE-SHT group demonstrated slightly higher estradiol levels and a modest numerical increase in FSH compared with placebo, although these changes were not statistically significant. LH levels remained stable, and total testosterone showed only a minor numerical increase. The absence of significant between-group differences suggests that the intervention did not meaningfully alter the hypothalamic-pituitary-gonadal (HPG) axis. From a clinical perspective, this is reassuring, as it indicates that the mood and quality-of-life benefits observed with SHT and ARE-SHT were not driven by major hormonal shifts, but rather through alternative mechanisms (e.g., adaptogenic, stress-modulating, or neuroendocrine pathways). Importantly, the stability of standard laboratory parameters further supports the safety of the intervention (11).

This study is robust as it employs a comparative analysis, allowing for a clear understanding of both the additive and individual effects of ARE and SHT. The observed additive effects of the ARE and SHT combination may be explained by the complementary pharmacological activities of both. ARE is well established as an adaptogen with the ability to modulate the HPA axis, balance cortisol levels, and improve stress resilience. It also exhibits neuroprotective and anti-inflammatory effects, which are related to improved mood and overall well-being. Whereas SHT contains steroidal saponins with phytoestrogenic activity, along with potent antioxidant and immunomodulatory properties, supporting hormonal balance and alleviation of vasomotor and urogenital symptoms in menopause. When administered together, these agents may act on both neuroendocrine and estrogenic pathways, thereby providing broader and more effective relief of menopausal symptoms than either intervention alone.

The three-arm study design is a cost-effective and time-efficient approach for evaluating multiple conditions simultaneously. There were no significant changes in safety parameters, and participants reported only mild adverse events, indicating that both the combination of ARE-SHT and SHT alone are safe and well-tolerated.

However, some limitations must be considered. Self-reporting bias may have influenced participants' reporting of adverse events, as they may have underreported or overreported symptoms based on personal perceptions. The study duration of 8 weeks, while adequate for assessing short-term efficacy and safety, limits conclusions regarding the sustained benefits and long-term safety of the intervention. Although the study was sufficiently powered for the primary outcomes, the sample size was relatively small and participants were recruited from specific geographic regions, which may limit the generalizability of the findings to broader and more diverse populations. The small sample size limited the feasibility of subgroup analyses by menopausal stage. Potential confounding influences from participants' diet, lifestyle, or physical activity were not systematically controlled, and although only mild adverse events were observed. In addition, as no adjustment for multiple testing was applied to exploratory hormonal analyses, there remains a potential risk of type I error, and these findings should be considered hypothesis-generating. Although FSH levels were measured, they were not systematically used to confirm the menopausal stage, which may limit the precision of participant characterization. Future studies with larger sample sizes, longer follow-up periods, and specific menopausal stages are warranted to evaluate the durability of effects and to identify any delayed adverse events.

The Shatavari root extract demonstrated significant reductions in MRS and PSS scores. While improvements in MENQOL scores, hot flashes, and hormonal changes were observed as trends, these did not reach statistical significance and therefore warrant confirmation in larger, longer-term studies. No changes in hepatic and renal markers were reported. There were no significant adverse events reported, indicating it is a safe and effective herbal option. However, the combination with Ashwagandha also showed improvement in most of the parameters as compared to Shatavari alone. Thus, Shatavari was found to be more effective alone and in combination with Ashwagandha in managing menopausal symptoms and in enhancing overall health, well-being, and quality of life in women with menopause. Future well-designed trials with larger and more diverse populations, extended follow-up durations, and incorporation of mechanistic biomarker assessments are recommended to confirm these findings and better understand the long-term efficacy and safety of Shatavari and its combinations.