Rewiring Fear and Worry: A Holistic Approach to Conquering Anxiety in the Female Patient – Jonathan E. Prousky, ND, MSc, MA

Rewiring Fear and Worry: A Holistic Approach to Conquering Anxiety in the Female Patient ​

Dr. Jonathan E. Prousky, ND, MSc, MA

Evidence-Based Strategies for Managing Anxiety in Women: Hormonal and Natural Treatments

Abstract

This paper examines the prevalence, hormonal contributors, and integrative treatment strategies for anxiety disorders in women, emphasizing a holistic, patient-centered approach. ​Anxiety disorders, including generalized anxiety disorder, panic disorder, specific phobias, and social anxiety disorder, are more common in women, influenced by hormonal changes during puberty, menstrual cycles, pregnancy, and menopause. ​ Progesterone It is also reported to have anticonvulsant, memory-enhancing, and sedative properties, 

and its metabolite allopregnanolone plays key roles in modulating anxiety through its interaction with the gamma-aminobutyric acid type A receptor. ​The paper reviews integrative treatments such as bioidentical transdermal progesterone cream, which helps regulate emotions and modulate the hypothalamic-pituitary-adrenal axis. Nutraceuticals like 5-hydroxytryptophan and botanical medicines, including proprietary blends of Magnolia officinalis and Phellodendron amurense, as well as Saffron and Rhodiola extracts, are discussed for their anxiety-reducing properties. Lavender extract and Maca extract are also highlighted for their effectiveness. ​Mind-body techniques, including Mindful Self-Compassion and Emotional Freedom Techniques, are presented as valuable tools for managing anxiety. ​The paper concludes that a multifaceted, integrative approach combining nutraceuticals, botanical medicines, bioidentical progesterone, and mind-body techniques can effectively manage anxiety in women, promoting lasting wellness and freedom from anxiety. 

Introduction

This paper investigates the prevalence, key hormonal contributors, and integrative treatment strategies for anxiety disorders in women, highlighting the significance of a holistic, patient-centered approach. By analyzing the impact of hormonal fluctuations and neurobiological factors that contribute to the development of anxiety disorders in women, this paper provides practical, evidence-based strategies for effective management.

Prevalence, Types of Anxiety Disorders, and Hormonal Influences ​

In a review article, Hansloo and Epperson described the different types of anxiety disorders that are more prevalent among females, including how different stages during the female lifespan (i.e., from puberty to postmenopausal periods) are impacted by hormonal fluctuations and other factors.1 Anxiety disorders, including generalized anxiety disorder (GAD), panic disorder (PD), specific phobias, and social anxiety disorder (SAD), are more prevalent in women than men. ​Females have higher rates of lifetime diagnosis for almost all types of anxiety disorders. Core features of these disorders include subjective anxiety or fear experience, physiological reactivity, and avoidance behavior. ​

Hansloo and Epperson also discussed the roles that ​hormonal fluctuations have in the development and exacerbation of anxiety disorders in women.1 The hormonal changes that initiate puberty are linked to the etiology of anxiety disorders, and this period is also marked by increased psychosocial stress. ​Puberty represents a vulnerable developmental window for the occurrence of anxiety disorders, with higher rates among girls as they enter adolescence. ​Ovarian steroids and their metabolites are neuroactive, and hormonal changes during the menstrual cycle, pregnancy, and menopause significantly impact anxiety levels. ​ For instance, some 80% of women experience at least one physical, mood, or anxiety symptom in the luteal phase, and 20% experience premenstrual symptoms. Women with anxiety disorders may also experience an exacerbation of their symptoms premenstrually. Additionally, 5% to 8% of women experience premenstrual dysphoric disorder (PMDD), which has a significant anxiety symptom component. ​

Is Progesterone Insufficiency, Deficiency, or Defects to Blame?

Progesterone and its metabolite, allopregnanolone (ALLO), can bind to the gamma-aminobutyric acid type A (GABA-A) receptor.2 This binding enhances the receptor’s sensitivity to GABA, increasing the influx of chloride ions into the neuron, which further hyperpolarizes the cell membrane and diminishes neuronal excitability.  Moreover, in the amygdala (i.e., a deep part of the brain that processes fearful and unpleasant stimuli), GABAergic neurotransmission attenuates the production of unhelpful emotional and behavioral responses, thereby lessening fear and anxiety.3 Consequently, this mechanism contributes to the sedative, anticonvulsive, and anxiolytic effects of progesterone, effectively moderating excitation within the nervous system.2

Altered interactions between ALLO and the GABA-A receptor contribute to anxiety disorders.1 Broadly speaking, dysfunction in the synthesis of ALLO may further impair GABAergic function, thereby increasing the risk of all psychiatric disorders.4 During the premenstrual luteal phase, if progesterone is low and the estradiol level is high, for example, there can be an associated increase in smoking, alcohol consumption, and body dissatisfaction.4 Research has shown an increase in anxiety symptom exacerbation premenstrually and increases in anxiety that results from stressful life experiences premenstrually.4  State and trait anxiety were associated with daily anxiety reports during the luteal phase.4 Additionally, the acoustic startle response, heightened among individuals with anxiety disorders, is elevated in the late luteal phase.4 

A report noted an increase of 300% or more in the prescription rates of psychotropics, hypnotics, and analeptics among women between 50 and 55 years of age.2 This increase in medication use among perimenopausal women is linked to the influence of progesterone and its metabolites on neurological and psychological functions. During perimenopause, women undergo significant hormonal changes, significantly declining progesterone levels. Progesterone and its metabolites interact with the central nervous system, notably through GABA receptors (as noted above). These interactions can affect mood, anxiety, and neurological conditions, resulting in a heightened need for medications to address these symptoms.2 The perimenopause duration eventually passes into menopause, culminating into postmenopause, which is associated with lower ALLO and progesterone levels compared to premenopausal women.5 

Integrative Treatment Approaches ​

A holistic approach to managing anxiety in women includes bioidentical progesterone, specific nutraceuticals, botanical medicines, and key mind-body techniques. This section reviews evidence-based integrative treatments and their mechanisms of action, focusing on studies with predominantly female subjects and highlighting only anxiety outcomes. Adverse effects will not be discussed in detail, as they were generally insignificant in the cited studies.

Bioidentical Transdermal Progesterone Cream (BTPC)

Progesterone is converted into ALLO via a two-step enzymatic process in the brain.6 Therefore, BTPC plays an essential role in managing anxiety in women. ​BTPC’s metabolite, ALLO, a potent positive allosteric modulator of the GABA-A receptor,1 helps regulate emotion, promote neurogenesis, and modulate the hypothalamic-pituitary-adrenal (HPA) axis.7

Even though high doses of progesterone exhibit anxiolytic and sedative effects,8 physiologic doses of progesterone delivered via BTPC may serve as an effective treatment for anxiety, especially in premenopausal and postmenopausal women. When using BTPC among premenopausal females, it should be taken at bedtime for 15 days each month at a dose of 20 mg/day on days 12 to 26 (i.e., day 1 being the onset of menses).9 In premenopausal females with longer cycles, taking BTPC for a longer duration on days 10 to 28 of the menstrual cycle is usually necessary. Sometimes, the dose must be increased to 30 mg/day for more durable therapeutic effects.9 

The dose of BTPC for postmenopausal females is 20 mg/day (i.e., taken at bedtime) based on studies that have shown reductions in menopausal symptoms.9-12 Postmenopausal patients should take a rest day, so the application is 6 days each week, except on Sundays.9 The late physician Dr. Jonathan R. Lee, when discussing the therapeutic application of BTPC, noted that it results in more restful sleep, with patients feeling more refreshed in the morning while helping to modulate stress.9

5-hydroxytryptophan (5-HTP)

Like fear, worry is another salient construct implicated in GAD and other anxiety disorders, especially when reconciling uncertainty becomes too tricky to manage emotionally. Serotonin (5-HT) circuitry is widely implicated in GAD. The positive results from selective serotonergic reuptake inhibitors (SSRIs) upon GAD symptoms strongly suggest that serotonin moderates worry and other symptoms.13 Evidence from functional brain imaging studies has shown that midbrain serotonin transporter (SERT) density is negatively correlated with symptom severity in GAD, suggesting that lower SERT density is associated with more severe anxiety symptoms.14  

Given the importance of reducing worry in female patients, 5-HTP is worth considering due to its ability to enter the bloodstream, cross the blood-brain barrier, and increase serotonin levels.15 An open-label pilot study involved 15 adult women with major depressive disorder who did not respond to SSRIs or serotonin-norepinephrine reuptake inhibitors (SNRIs).16 They took 200 mg/day of 5-HTP and five g/day of creatine monohydrate alongside their standard antidepressant doses for 8 weeks. Results showed a significant reduction in mean Beck Anxiety Inventory (BAI) scores, from 22.7 ± 9.2 to 9.3 ± 6.4 (p<0.00001), indicating over a 50% decrease in anxiety. The treatment was well-tolerated, with no serious adverse events reported. A slow- or timed-release formulation of 5-HTP is recommended for optimal results, as it provides more consistent elevation of brain extracellular 5-HT levels.17 My clinical experience suggests a daily dosage of 200-800 mg of 5-HTP is effective in alleviating worry and anxiety symptoms.

Proprietary Blend (PB) Containing Extracts of Magnolia officinalis and Phellodendron amurense 

The PB was studied in a pilot randomized controlled trial (RCT) involving healthy, overweight premenopausal women (ages 20-50) who reported increased eating in response to stress and elevated anxiety scores.18 Participants received 500 mg of PB twice daily for 6 weeks. While PB did not significantly reduce long-standing anxiety or depression, the average decrease in the Spielberger STATE Anxiety Questionnaire score was nearly double in the PB group compared to the placebo group. STATE Anxiety is a temporary emotional state marked by physiological arousal and feelings of apprehension, dread, and tension. Initial STATE Anxiety levels were 32.5 ± 7.6 for PB and 29.4 ± 6.7 for placebo. The average reductions were -14.3 ± 12.1 for PB and -7.6 ± 9.8 for placebo, with a significant difference favoring PB (p=0.045).

Another RCT examined the effects of the same PB on cortisol levels and mood in moderately stressed individuals, involving 56 participants (35 men and 21 women).19 Subjects ingested 500 mg/day of PB for 4 weeks. At the trial’s end, the PB group showed a significant reduction in salivary cortisol levels (−18%) compared to placebo. Additionally, the PB group reported lower overall stress (11%), tension (13%), depression (20%), anger (42%), fatigue (31%), and confusion (27%), along with higher vigor (18%) and global mood state (11%). These improvements were statistically significant (p<0.05), indicating a positive impact of PB on mood and well-being. The therapeutic effects of PB likely involve the modulation of neurotransmitters and stress-related pathways, contributing to its anti-stress and anxiolytic properties. In my clinical experience with this PB, daily doses of 500 to 1000 mg are necessary to achieve observable therapeutic effects.

Saffron Extract as Monotherapy or in Conjunction with Rhodiola Extract

A pilot clinical trial investigated the efficacy of Crocin, the main active component of saffron extract, as an adjunctive treatment for major depressive disorder (MDD).20 Crocin influences levels of key neurotransmitters in the brain, including dopamine, norepinephrine, and serotonin, which are vital for mood regulation and mental well-being. It is also reported to have anticonvulsant, memory-enhancing, and sedative properties, contributing to its potential therapeutic effects on central nervous system disorders.

The study involved 40 MDD patients aged 24 to 50 years (34 females and six males), with a mean age of 36.2 years.20 The treatment group received 30 mg/day of Crocin (15 mg twice daily) alongside an SSRI, while the placebo group received placebo tablets with an SSRI. The study lasted 4 weeks. Initial baseline scores for the Beck Anxiety Inventory (BAI) were shown in the figures, with the Crocin group averaging 38 and the placebo group averaging 36. After the trial, the Crocin group showed a significant improvement in BAI scores, with an average decrease of 12.7, compared to a decrease of 2.6 in the placebo group (p<0.0001).

An RCT evaluated the therapeutic efficacy of Saffron as a treatment for both anxiety and depression.21 The study group comprised 22 women and eight men, while the control group included 20 women and ten men. The average age of the study group was 42.8 years, and the average age of the control group was 43.6 years. The study group received a 50 mg Saffron capsule twice daily for 12 weeks, while the control group received a matched placebo capsule. The study found a significant difference in anxiety between the Saffron group and the placebo group at the 12-week time point (p<0.001). The Saffron group demonstrated a statistically significant improvement in BAI scores compared to the placebo group. The difference in BAI scores at the endpoint (week 12) compared to baseline was -8.65 ± 2.59 for the Saffron group and -5.46 ± 2.82 for the placebo group. Unfortunately, baseline or pre-treatment scores were not provided in the study.

In another study, participants were supplemented with a fixed combination of Rhodiola and Saffron extracts in a dietary supplement containing 154 mg of Rhodiola Extract and 15 mg of Saffron Extract per tablet.22 The mechanism of Saffron Extract was noted earlier when discussing Crocin. Rhodiola Extract helps the body adapt to stress while promoting resilience, and it also modulates the levels of neurotransmitters such as 5-HT, dopamine, and norepinephrine. The recommended dose of this supplement was two tablets per day for 6 weeks. The study included 59 patients screened and enrolled by 16 general practitioners between November 2016 and March 2017. The study had the most female participants, comprising 82.2% of the safety population and 81.1% of the per-protocol population. There was a significant decrease in Hospital Anxiety and Depression Scale (HADS) anxiety scores after 6 weeks of supplementation with the combination of herbal extracts. The reduction in anxiety scores was noted starting from 2 weeks of supplementation and continued until the end of the study, indicating a decrease in anxiety symptoms and severity among participants. The reduction in HADS anxiety scores was 31.3%, from 12.0±3.1 on Day 0 to 8.0±3.2 on Day 42, with a mean difference of 3.9 ±3.3 (p<0.0001). When using Saffron Extract as monotherapy or combined with Rhodiola Extract, the recommended daily dose for Saffron Extract is 30 to 50 mg. The daily dose for Rhodiola Extract should be 300 to 500 mg.

Lavender (Silexin) Extract

A 6-week randomized controlled trial (RCT) compared the effectiveness of Lavender Extract (Silexan) to Lorazepam.23 78 male and female patients participated, but the specific gender breakdown was not provided. The treatments compared were Silexan (80 mg), a lavender oil capsule preparation, and Lorazepam (0.5 mg), a benzodiazepine. Both Silexan and Lorazepam target the GABA system, which is crucial for regulating anxiety and stress responses in the brain. The Hamilton Anxiety Rating Scale (HAM-A) total score was 25±4 points for both groups at baseline. At 6 weeks, HAM-A scores decreased by 11.3±6.7 points in the Silexan group and 11.6±6.6 points in the Lorazepam group, with all results being statistically significant (p=0.04). The responder rate, defined as a reduction of the HAM-A total score by at least 50%, was higher in the Silexan group (52.5%) than the Lorazepam group (40.5%). The remission rate, defined as a HAM-A total score below 10 points, was also higher in the Silexan group (40%) versus the Lorazepam group (27%).

A 10-week RCT compared the effectiveness of Lavender Extract (Silexan) to Paroxetine (i.e., an SSRI) in 523 patients with GAD, comprising a much higher percentage of female subjects.24 Silexin was chosen since it regulates neuronal excitability in the hippocampus, a key limbic structure linked to emotions and stress, where abnormalities are associated with anxiety disorders. Baseline HAM-A scores were 26.0±4.5 for Silexan (160 mg/day), 25.8±4.8 for Silexan (80 mg/day), 25.8±4.9 for Paroxetine (20 mg/day), and 25.1±4.7 for placebo. ​By the end of the study, HAM-A score reductions were -14.1±9.3 for Silexan (160 mg/day), -12.8±8.7 for Silexan (80 mg/day), -11.3±8.0 for Paroxetine (20 mg/day), and -9.5±9.0 for placebo, with all results achieving statistical significance (p<0.001). ​The results showed convincing anxiolytic effects from 160 mg/day of Silexin, comparable to Paroxetine. The results also demonstrated that Silexin can be terminated abruptly at the end of 10 weeks without any symptoms of withdrawal. 

My clinical experience has shown that the only effective dose of Lavender Extract for alleviating anxiety symptoms is 160 mg/day. However, I have used daily doses as high as 640 mg with good clinical results with several patients. 

Maca (Lepidium peruvianum) Extract

A clinical trial (Trial II) on postmenopausal women examined the effects of Maca capsules (2000 mg daily) for eight months.25 Results showed hormonal improvements, including decreased follicle-stimulating hormone (FSH), increased luteinizing hormone (LH), progesterone, and estradiol. Menopausal symptoms are significantly reduced, such as fatigue, muscle and joint aches, night sweats, sleep disturbances, and decreased libido. Greene’s Menopausal Test Score indicated a decrease in excessive alertness and sudden anxiety, with the latter change being indicative of an improvement in state anxiety. While these findings suggest Maca’s potential to alleviate menopausal symptoms and anxiety, further research is necessary to confirm its efficacy.

A randomized, crossover trial was conducted on 16 healthy postmenopausal women aged 50-60 to assess the effects of six weeks of Maca supplementation on psychological symptoms, sexual function, and hormone levels.26 Participants consumed either 3.5 grams of Maca powder or a placebo daily for six weeks, followed by a two-week washout period. The Maca powder, provided in individual sachets, was mixed with water or juice and taken once daily. This dosage was based on previous human studies. The study measured serum levels of estradiol, FSH, LH, and sex-hormone binding globulin but found no significant changes between baseline, Maca treatment, and placebo. Using Greene’s Menopausal Test Score, significant reductions were observed in psychological symptoms, including anxiety, depression, and sexual problems. Maca supplementation significantly reduced anxiety and depression symptoms compared to baseline and placebo. Specifically, there was a 30.8% reduction in anxiety symptoms and a 28.9% reduction in depression symptoms. The anxiety subscale, which includes items like heart palpitations, nervousness, sleep disturbances, and panic attacks, showed a significant improvement. All these changes were statistically significant (p-values<0.05). 

I typically recommend 2000 mg daily to achieve sufficient therapeutic outcomes with MACA supplementation.  

Red Clover Extract (RCE) 

This was a 180-day RCT involving 109 postmenopausal women (average age 53.5 years).27 Participants were randomly assigned to receive either RCE or a placebo for 90 days. Participants in Group A received two daily capsules containing 80 mg of RCE, while Group B received a placebo. This treatment regimen lasted for 90 days, followed by a 7-day washout period, and then 90 more days of the opposite treatment. RCE is believed to work through their estrogenic actions, antioxidant properties, and anti-inflammatory effects. The isoflavones in RCE can weakly mimic estrogen, potentially alleviating menopausal symptoms. Before treatment, participants had elevated levels of anxiety and depression, as measured by the HADS and the Zung Self-Rating Depression Scale (SDS). After 90 days of RCE treatment, participants experienced a significant reduction in anxiety and depression symptoms. The HADS total score decreased from 16.89 to 3.91, the anxiety subscale score from 9.98 to 2.40, and the depression subscale score from 6.91 to 1.50. Similarly, the SDS score dropped from 12.24 to 2.37. Overall, RCE treatment resulted in significant reductions in anxiety and depression symptoms. The total HADS score decreased by 76.9%, with a 76% reduction in the anxiety subscale and a 78.3% reduction in the depression subscale. These findings suggest that RCE may be an effective treatment for reducing menopausal symptoms related to anxiety and depression.

I commonly recommend 80 mg of RCE at bedtime to achieve therapeutic results among postmenopausal anxious patients. I often combine RCE with BTPC to achieve better clinical outcomes.  

Mindful Self-Compassion (MSC)

MSC is associated with positive psychological outcomes and reduced psychopathology.28 Research indicates that individuals who practice self-compassion tend to experience lower levels of depression, anxiety, and stress. Additionally, MSC is linked to positive psychological strengths like happiness, emotional intelligence, optimism, wisdom, curiosity, and initiative and has been shown to protect against eating disorders and body dissatisfaction. To enhance MSC, I often guide patients through its three core components: self-kindness, common humanity, and mindfulness. Self-kindness involves treating oneself with empathy and understanding, much like a caring friend. Common humanity acknowledges that everyone experiences suffering and imperfection. Mindfulness entails recognizing emotions without judgment and avoiding overidentification with them. For instance, when a patient named Jennifer feels overwhelmed, a clinician might encourage Jennifer to say the following to herself, “Jennifer, it’s understandable to feel overwhelmed. We all have moments like this. Remember, you can get through this, and I’m here to support you.” Patients can incorporate physical self-soothing techniques, such as a gentle arm squeeze or a hand on the heart, to enhance the benefits of this brief MSC exercise.29 This simple act can trigger the release of oxytocin, promoting feelings of trust, calm, safety, and connection. This practice should be repeated multiple times daily to maximize the therapeutic impact, especially when emotions feel overwhelming.

Emotional Freedom Technique (EFT)

EFT combines acupuncture and psychology to release emotional pain and create positive self-beliefs. ​ It involves tapping on specific acupressure points while focusing on the issue and using verbal affirmations. A study involving 203 participants, primarily women over 50, underwent 6 EFT workshops.30 This mental health intervention led to significant improvements in anxiety (-40%), depression, PTSD, pain, and cravings while also increasing happiness (all p-value  0.000). Additionally, physiological markers of health, such as blood pressure (systolic blood pressure -6%, p=0.001; diastolic blood pressure -8%, p<0.000) and salivary cortisol levels (-37%, p<0.000), significantly decreased after EFT treatment.

A study involving 22 German-speaking anxiety patients (15 female, seven male) compared the effects of EFT and progressive muscle relaxation (PMR) on emotional processing.31 Both interventions reduced the Late Positive Potential (LPP) in the brain’s left centro-parietal areas while processing negative emotions. However, the specific effects differed: EFT primarily modulated the processing of angry stimuli, while PMR mainly affected the processing of fearful stimuli. These findings suggest that both interventions can enhance emotion regulation by reducing arousal in response to negative emotions.

Although I do not use EFT in my naturopathic mental health practice, I provide patients with information on it and advise them to download the app The Tapping Solution (https://www.thetappingsolution.com/). This app offers free guided EFT sessions that can be used several times daily to improve emotional regulation. Many patients find EFT to be a helpful tool for managing stress and anxiety alongside their naturopathic treatment plan. 

Conclusion

Anxiety in women is a serious issue that requires a multifaceted, integrative approach to treatment. ​ By unlocking the power of nutraceuticals, botanical medicines, bio-identical hormones, and mind-body techniques, healthcare providers can help female patients overcome debilitating anxiety. ​By rewiring the brain to become more resilient against persistent fears and worries, these practical, evidence-based tools can empower patients and guide them toward lasting wellness and freedom from anxiety. 

References

1. Hantsoo L, Epperson CN. Anxiety Disorders Among Women: A Female Lifespan Approach. Focus (Am Psychiatr Publ). 2017;15(2):162-172. doi:10.1176/appi.focus.20160042 
2. Gruber DM, Sator MO, Wieser F, Worda C, Huber JC. Progesterone and neurology. Gynecol Endocrinol. 1999;13 Suppl 4:41-45. doi:10.1080/gye.13.s4.41.45
3. Jie F, Yin G, Yang W, et al. Stress in Regulation of GABA Amygdala System and Relevance to Neuropsychiatric Diseases. Front Neurosci. 2018;12:562. Published 2018 Aug 14. doi:10.3389/fnins.2018.00562
4. Handy AB, Greenfield SF, Yonkers KA, Payne LA. Psychiatric Symptoms Across the Menstrual Cycle in Adult Women: A Comprehensive Review. Harv Rev Psychiatry. 2022;30(2):100-117. doi:10.1097/HRP.0000000000000329
5. Kimball A, Dichtel LE, Nyer MB, et al. The allopregnanolone to progesterone ratio across the menstrual cycle and in menopause. Psychoneuroendocrinology. 2020;112:104512. doi:10.1016/j.psyneuen.2019.104512
6. Guennoun R, Labombarda F, Gonzalez Deniselle MC, Liere P, De Nicola AF, Schumacher M. Progesterone and allopregnanolone in the central nervous system: response to injury and implication for neuroprotection. J Steroid Biochem Mol Biol. 2015;146:48-61. doi:10.1016/j.jsbmb.2014.09.001 
7. Schüle C, Nothdurfter C, Rupprecht R. The role of allopregnanolone in depression and anxiety. Prog Neurobiol. 2014;113:79-87. doi:10.1016/j.pneurobio.2013.09.003 
8. Morssinkhof MWL, van Wylick DW, Priester-Vink S, et al. Associations between sex hormones, sleep problems and depression: A systematic review. Neurosci Biobehav Rev. 2020;118:669-680. doi:10.1016/j.neubiorev.2020.08.006
9. Lee JR, Hopkins V. What your doctor may not tell you about menopause: The breakthrough book on natural progesterone. Time Warner Company; 1996.
10. Leonetti HB, Landes J, Steinberg D, Anasti JN. Transdermal progesterone cream as an alternative progestin in hormone therapy. Altern Ther Health Med. 2005;11(6):36-38.
11. Leonetti HB, Longo S, Anasti JN. Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss. Obstet Gynecol. 1999;94(2):225-228. doi:10.1016/s0029-7844(99)00266-5.
12. Stephenson K, Neuenschwander PF, Kurdowska AK, Pinson B, Price C. Transdermal progesterone: Effects on menopausal symptoms and on thrombotic, anticoagulant, and inflammatory factors in postmenopausal women. Int J Pharm Compd. 2008;12(4):295-304.
13. Vaswani M, Linda FK, Ramesh S. Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive review. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27(1):85-102. doi:10.1016/s0278-5846(02)00338-x
14. Martin EI, Ressler KJ, Binder E, Nemeroff CB. The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. Clin Lab Med. 2010;30(4):865-891. doi:10.1016/j.cll.2010.07.006
15. Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998;3(4):271-280.
16. Kious BM, Sabic H, Sung YH, Kondo DG, Renshaw P. An Open-Label Pilot Study of Combined Augmentation With Creatine Monohydrate and 5-Hydroxytryptophan for Selective Serotonin Reuptake Inhibitor- or Serotonin-Norepinephrine Reuptake Inhibitor-Resistant Depression in Adult Women. J Clin Psychopharmacol. 2017;37(5):578-583. doi:10.1097/JCP.0000000000000754 
17. Jacobsen JPR, Krystal AD, Krishnan KRR, Caron MG. Adjunctive 5-Hydroxytryptophan Slow-Release for Treatment-Resistant Depression: Clinical and Preclinical Rationale. Trends Pharmacol Sci. 2016;37(11):933-944. doi:10.1016/j.tips.2016.09.001
18. Kalman DS, Feldman S, Feldman R, et al. Effect of a proprietary Magnolia and Phellodendron extract on stress levels in healthy women: A pilot, double-blind, placebo-controlled clinical trial. Nutr J. 2008;7:11. doi:10.1186/1475-2891-7-11.
19. Talbott SM, Talbott JA, Pugh M. Effect of Magnolia officinalis and Phellodendron amurense (Relora®) on cortisol and psychological mood state in moderately stressed subjects. J Int Soc Sports Nutr. 2013;10(1):37. doi:10.1186/1550-2783-10-37.
20. Talaei A, Hassanpour Moghadam M, Sajadi Tabassi SA, Mohajeri SA. Crocin, the main active saffron constituent, as an adjunctive treatment in major depressive disorder: A randomized, double-blind, placebo-controlled, pilot clinical trial. J Affect Disord. 2015;174:51-56. doi:10.1016/j.jad.2014.11.035.
21. Mazidi M, Shemshian M, Mousavi SH, et al. A double-blind, randomized and placebo-controlled trial of saffron (Crocus sativus L.) in the treatment of anxiety and depression. J Complement Integr Med. 2016;13(2):195-199. doi:10.1515/jcim-2015-0043.
22. Bangratz M, Ait Abdellah S, Berlin A, et al. A preliminary assessment of a combination of rhodiola and saffron in the management of mild-moderate depression. Neuropsychiatr Dis Treat. 2018;14:1821-1829. doi:10.2147/NDT.S169575.
23. Woelk H, Schläfke S. A multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder. Phytomedicine. 2010;17(2):94-99. doi:10.1016/j.phymed.2009.10.006
24. Kasper S, Gastpar M, Müller WE, et al. Lavender oil preparation Silexan is effective in generalized anxiety disorder—a randomized, double-blind comparison to placebo and paroxetine. Int J Neuropsychopharmacol. 2014;17(6):859-869. doi:10.1017/S1461145714000017.
25. Meissner HO, Kapczynski W, Mscisz A, Lutomski J. Use of gelatinized maca (Lepidium peruvianum) in early postmenopausal women. Int J Biomed Sci. 2005;1(1):33-45.
26.  Brooks NA, Wilcox G, Walker KZ, et al. Beneficial effects of Lepidium meyenii (Maca) on psychological symptoms and measures of sexual dysfunction in postmenopausal women are not related to estrogen or androgen content. Menopause. 2008;15(6):1157-1162. doi:10.1097/gme.0b013e3181732953.
27.  Lipovac M, Chedraui P, Gruenhut C, et al. Improvement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from red clover extracts. Maturitas. 2010;65(3):258-261. doi:10.1016/j.maturitas.2009.10.014.
28. Albertson ER, Neff KD, Dill-Shackleford KE. Self-compassion and body dissatisfaction in women: A randomized controlled trial of a brief meditation intervention. Mindfulness. 2015;6(3):444-454. doi:10.1007/s12671-014-0277-3.
29. Neff K. Self-compassion: Stop beating yourself up and leave insecurity behind. HarperCollins Publishers; 2011.
30. Bach D, Groesbeck G, Stapleton P, et al. Clinical EFT (Emotional Freedom Techniques) improves multiple physiological markers of health. J Evid Based Integr Med. 2019;24:2515690X18823691. doi:10.1177/2515690X18823691.
31. König N, Steber S, Seebacher J, et al. How therapeutic tapping can alter neural correlates of emotional prosody processing in anxiety. Brain Sci. 2019;9(8):206. doi:10.3390/brainsci9080206.