PLMI Blog

The menstrual cycle is a complex interaction of hormonal signals involving estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Hormonal balance is crucial for overall well-being, affecting everything from energy levels to fertility, vitality, and metabolic, immune, bone, and emotional health. Imbalances, however, can disrupt these essential processes. Understanding the impacts of imbalances and where women are in their cycle is informative and empowering for enhancing their health, vitality, and well-being.

A CLOSER LOOK AT THE MENSTRUAL CYCLE

A woman’s cycle is mediated by a dynamic interplay among estradiol, progesterone, FSH, and LH. These hormones fluctuate throughout the varying phases of one’s cycle, guiding follicular development, ovulation, and the preparation of the endometrium for potential implantation (1). The physiological effects of these hormonal shifts underscore their relevance to health.

By becoming more attuned to one’s body and hormonal shifts, women can foster a healthier relationship with themselves by implementing overall self-care strategies that align with their phase while reducing symptoms of hormonal imbalance.

The Role of The HPTAO Axis

A woman’s cycle is dynamic and continually changing in response to interactions of hormones secreted by the hypothalamus, pituitary gland, and ovaries. Fluctuations are influenced by the delicate balance of hormones within the psycho-neuroendocrine circuit, comprising the hypothalamic, pituitary, thyroid, adrenal, and ovarian axis (HPTAO axis). Understanding hormonal shifts and their effects on reproductive health, from fertility through menopause, is crucial for optimizing overall health and quality of life.

The hypothalamus-pituitary-ovary (HPO) axis is a primary modulator of female reproductive function. This regulation involves the hypothalamus releasing gonadotropin-releasing hormone (GnRH), which then stimulates the pituitary to secrete FSH and LH (2).

Each level of this neuroendocrine system operates via a complex and highly coordinated process. Modulation is influenced by hormone production levels and by the sensitivity of hormone receptors. Consequently, dysfunction at any level of the HPO axis affects the other levels as well (3). Chronic stress can contribute to estrogen insufficiency by activating these axes, having implications for these collective systems (4).

Cyclic Hormonal Patterns

Estradiol, progesterone, FSH, and LH play essential roles in modulating the menstrual cycle. Imbalances in these hormones can lead to impeded reproductive and overall health. Mounting research continues to deepen our understanding of these cyclic hormonal patterns and their impact, supporting more effective, personalized strategies for improved health and well-being (5).

Follicular Phase—Rise in Estrogen

The follicular phase initiates the first day of menstruation and ends at ovulation. Low concentrations of estradiol and progesterone trigger the pituitary gland to secrete and release follicle-stimulating hormone (FSH). FSH stimulates the growth and maturation of ovarian follicles. As these follicles develop, estradiol levels begin to increase, peaking just before ovulation. This rise in estradiol provides negative feedback to FSH secretion, resulting in a reduction of FSH levels as follicle development further progresses (1). Estrogen is dominant in this phase, influencing the vitality of skin, vascular, bone, and immune health.

Estradiol plays a key role in promoting ovulation and supporting implantation if fertilization occurs, with a profound impact on the reproductive system. It is also involved in modulating neurotransmitters, including dopamine and serotonin, significant for mood regulation. Insufficient amounts of estrogen, therefore, can impede these processes. Balanced levels of both estrogen and progesterone are vital for influencing reproductive and overall health (1, 5). In addition to maintaining the lining of the uterus, progesterone is significant for nervous system health, having neuroprotective and mood-modulating properties.

Ovulatory Phase—Surge in LH & FSH

During the mid-way point of a woman’s cycle, a peak in estradiol levels triggers a surge in luteinizing hormone (LH). This sudden increase in LH is crucial for ovulation, causing the mature follicle to release an egg. There is also an increase in follicle-stimulating hormone (FSH) during this time, supporting the final maturation of the ovum. The fleeting rise in estradiol and surge in LH are integral for successful ovulation, occurring roughly 10-12 hours following the LH peak.

LH is essential for ovulation and the formation of the corpus luteum, which produces progesterone. The increase in LH typically occurs 34-36 hours prior to ovulation. This surge also stimulates the luteinization of granulosa cells, in addition to the synthesis of progesterone, responsible for the mid-cycle increase in FSH (6).

The hypothalamic-pituitary-ovary axis plays a central role in modulating reproductive functions. This regulation is driven by the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, triggering the secretion of FSH and LH from the pituitary gland.

Luteal Phase—Preparing with Progesterone

Post-ovulation, the corpus luteum forms from the released egg and secretes progesterone and estradiol. Progesterone prepares the endometrium for potential implantation by thickening the uterine lining and increasing its glandular activity. Estradiol levels remain elevated to support this process. If implantation does not occur, the corpus luteum degenerates, leading to reduced levels of estradiol and progesterone and the shedding of the endometrial lining, or menstruation (1, 5).

IMPACTS OF IMBALANCE

Polycystic Ovary Syndrome (PCOS)

In PCOS, elevated levels of androgens and insulin resistance lead to disrupted hormonal patterns. Women with PCOS often exhibit elevated LH levels and reduced FSH, causing an imbalance that results in irregular ovulation and menstrual cycles. This can result in symptoms such as anovulation, amenorrhea, and infertility (7).

Endometriosis & Infertility

Endometriosis refers to the ectopic implantation of tissue lining the uterus outside of the uterine cavity, often resulting in pain and infertility (8). This condition is associated with abnormal estradiol levels and disrupted progesterone signaling. Elevated estradiol levels can exacerbate endometrial tissue growth, while insufficient progesterone can fail to adequately modulate the endometrial lining. Treatments targeting hormonal modulation, such as GnRH agonists, are often used to manage symptoms by suppressing estradiol production (9).

Hypothalamic Amenorrhea

Hypothalamic amenorrhea can result from excessive stress or exercise, as well as low body weight, leading to reduced secretion of GnRH from the hypothalamus. This reduction in GnRH decreases FSH and LH production from the pituitary, leading to low estradiol and progesterone levels and menstrual cessation. Addressing underlying causes, including emotional and physical stress, as well as nutritional deficiencies, can support restoring normal menstrual function and hormonal balance (10).

Altered Metabolic & Microbiome Health

The synchronicity of hormones plays a crucial role in regulating cellular metabolism and GI health. An imbalance can disrupt thyroid function and the body’s ability to process nutrients efficiently, leading to issues including weight gain, insulin resistance, and metabolic conditions. Hormonal imbalances can also alter the composition of the gut microbiome, leading to dysbiosis. This can result in inflammation, impeded digestion, absorption, and immune function, further impacting overall health (11).

Depleted Energy & Fatigue

Imbalances in hormones can result in chronic fatigue and low energy levels. High cortisol levels induced by stress can lead to adrenal fatigue, further contributing to a cycle of compromised sleep and heightened stress, exacerbating hormonal imbalances (12).

Emotional Dysregulation

Hormones are closely associated with mood and emotional regulation. Imbalances can result in mood swings, anxiety, depression, and irritability. Fluctuating estrogen levels can affect serotonin and dopamine production, impeding mood health. Emotional dysregulation can further contribute to difficulties in managing stress and interpersonal relationships and may further perpetuate poor mental health by disrupting sleep and activities of daily living (13).

Estradiol is pivotal in modulating neurotransmitter systems that influence neuronal circuits and brain functions, including learning, memory, reward, libido, and sexual health. This regulation involves serotonergic, dopaminergic, and glutamatergic signaling pathways. Estradiol and its receptors play significant roles in modulating these neurotransmitter signaling systems (14). In fact, reduced estrogen and elevated FSH levels have been associated with depression (15).

Compromised Skin & Libido

Hormone alterations influence skin health and libido. Imbalances can lead to acne, dryness, and premature aging. Low estrogen levels can cause a decline in collagen production, impacting skin elasticity. Similarly, imbalanced sex hormones can result in reduced libido (16, 17).

Modulators of Hormonal Health & What Can Impede It

While hormonal balance supports energy, fertility, vitality, metabolic, immune, bone, and emotional health, imbalances can compromise these processes.

WHOLE BODY APPROACH FOR BALANCE

Gaining insight into one’s cycle and hormonal shifts supports improved measures of self-care. Adequate nutrition, appropriate movement, detoxification, and sleep hygiene practices, as well as mitigating stress and environmental toxins, are imperative for hormonal balance.

Nutrition & Lifestyle

A balanced diet, sufficient in fiber, protein, complex carbs, leafy greens, and healthy fats are all ways of supporting hormonal balance. Seed cycling and adequate micronutrients are also significant. For such, zinc deficiency can impair the synthesis of both FSH and LH. Compellingly, reduced levels of zinc have also been observed in menopausal women with osteoporosis (18).

Vitamin D affects estrogen levels by maintaining calcium homeostasis and by increasing progesterone synthesis (19, 20). In otherwise healthy women, extremely low and high levels of body fat have been associated with reduced estrogen levels (21).

Adaptogens, a class of herbs, modulate the body’s response to stress and fatigue by interacting with the HPA axis. Maca is a promising adaptogen for modulating hormonal balance in women, supported by the literature (22).

Stress & Environmental Toxins

Environmental toxins, nutritional deficiencies, disrupted metabolic pathways, and lifestyle factors can influence any part of this tightly regulated and intricate system (23). Toxins from the environment can impede hormonal balance. As such, women exposed to pesticides and wood preservatives have been found to have lower levels of FSH (24). Chronic stress, as emphasized, wreaks havoc on the body and, notably, the HPA axis, impeding hormonal balance.

Optimizing Balance for Health & Well-being

You won’t want to miss this webinar –  A Woman’s Cycle of Life: Maximizing Outcomes through Mira and Femmenessence taking place on September 24th from 5 to 7 pm, PST with speakers Deanna Minich, PhD, CNS, IFMCP, Rosemary Anne Mackenzie, Stefani Kovacovsky Hayes, ND, LAC, and Jeffrey Bland, PhD.

These experts will delve further into women’s hormones, including estradiol, progesterone, FSH, and LH, to provide a thorough, personalized, and evidenced-based overview of hormone patterns. Patient case reports will be shared to showcase the benefits of empowering women to better understand their cycles, allowing providers to optimize individualized, targeted, and thoughtful treatment strategies. A clinically tested form of maca will also be reviewed for its efficacy in demonstrating statistically significant effects on hormones while notably supporting the HPATO axis.

References:

1. Reed BG, Carr BR. The Normal Menstrual Cycle and the Control of Ovulation. [Updated 2018 Aug 5]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279054/
2. Syrenicz J, Krzyscin M, Sowinska-Przepiera E. Relationships between hormonal parameters, body fat distribution and bone mineral density in women with psychogenic functional hypothalamic amenorrhea. Ginekol Pol. 2021;92(11):753-759. doi: 10.5603/GP.a2021.0041. Epub 2021 Apr 29. PMID: 33914322.
3. Petraglia F, Musacchio C, Luisi S, et al. Hormone-dependent gynecological disorders: a pathophysiological perspective for appropriate treatment. Best Pract Res Clin Obstet Gynaecol. 2008 Apr; 22 (2): 235- 49.
4. Abraham Gnanadass S, Divakar Prabhu Y, Valsala Gopalakrishnan A. Association of metabolic and inflammatory markers with polycystic ovarian syndrome (PCOS): an update. Arch Gynecol Obstet. 2021 Mar;303(3):631-643. doi: 10.1007/s00404-020-05951-2. Epub 2021 Jan 13. PMID: 33439300.
5. Tsamantioti ES, Mahdy H. Endometriosis. [Updated 2023 Jan 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK567777/
6. Bouic PJ. Endometriosis and infertility: the hidden link between endometritis, hormonal imbalances and immune dysfunctions preventing implantation! JBRA Assist Reprod. 2023 Jun 22;27(2):144-146. doi: 10.5935/1518-0557.20230015. PMID: 37348006; PMCID: PMC10279451.
7. Saadedine M, Kapoor E, Shufelt C. Functional Hypothalamic Amenorrhea: Recognition and Management of a Challenging Diagnosis. Mayo Clin Proc. 2023 Sep;98(9):1376-1385. doi: 10.1016/j.mayocp.2023.05.027. PMID: 37661145; PMCID: PMC10491417.
8. Cao W, Fu X, Zhou J, Qi Q, Ye F, Li L, Wang L. The effect of the female genital tract and gut microbiome on reproductive dysfunction. Biosci Trends. 2024 Jan 30;17(6):458-474. doi: 10.5582/bst.2023.01133. Epub 2023 Dec 17. PMID: 38104979.
9. Tomic S, Brkic S, Lendak D, Maric D, Medic Stojanoska M, Novakov Mikic A. Neuroendocrine disorder in chronic fatigue syndrome. Turk J Med Sci. 2017 Aug 23;47(4):1097-1103. doi: 10.3906/sag-1601-110. PMID: 29154201.
10. Toffoletto S, Lanzenberger R, Gingnell M, Sundström-Poromaa I, Comasco E. Emotional and cognitive functional imaging of estrogen and progesterone effects in the female human brain: a systematic review. Psychoneuroendocrinology. 2014 Dec;50:28-52. doi: 10.1016/j.psyneuen.2014.07.025. Epub 2014 Aug 13. PMID: 25222701.
11. Bendis PC, Zimmerman S, Onisiforou A, Zanos P, Georgiou P. The impact of estradiol on serotonin, glutamate, and dopamine systems. Front Neurosci. 2024 Mar 22;18:1348551. doi: 10.3389/fnins.2024.1348551. PMID: 38586193; PMCID: PMC10998471.
12. Young, EA, Midgley AR, Calrson NE. Alteration in the hypothalamic-pituitary-ovarian axis in depressed women. Arch Gen Psychiatry. 2000 Dec, 57 (12): 1157-62.
13. Pondeljak N, Lugović-Mihić L. Stress-induced Interaction of Skin Immune Cells, Hormones, and Neurotransmitters. Clin Ther. 2020 May;42(5):757-770. doi: 10.1016/j.clinthera.2020.03.008. Epub 2020 Apr 7. PMID: 32276734.
14. Minkin MJ. Menopause: Hormones, Lifestyle, and Optimizing Aging. Obstet Gynecol Clin North Am. 2019 Sep;46(3):501-514. doi: 10.1016/j.ogc.2019.04.008. Epub 2019 Jun 21. PMID: 31378291.
15. Bedwal RS, Bahuguna A. Zinc, copper and selenium in reproduction. 1994; 50: 626-40.
16. Kinuta K, Tanka H, Moriwake T. Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads. Endocrinology. 2000 Apr; 141 (4): 1317-24.
17. Barrea D, Avila E, Hernandez G, et al. Estradiol and progesterone synthesis in human placenta is stimulated by calcitrol. J Steroid Biochem Mol Biol. 2007 Mar; 103 (3-5). 529-32.
18. Ziomkiewicz A, Ellison PT, Lipson SF, et al. Body fat, energy balance and estradiol levels: a study based on hormonal profiles from complete menstrual cycles. Hum Reprod. 2008. No; 23 (11): 2555-63.
19. Uto-Kondo H, Naito Y, Ichikawa M, Nakata R, Hagiwara A, Kotani K. Antioxidant activity, total polyphenol, anthocyanin and benzyl-glucosinolate contents in different phenotypes and portion of Japanese Maca (Lepidiummeyenii). 2024 Jun 10;10(12):e32778. doi: 10.1016/j.heliyon.2024.e32778. PMID: 38975202; PMCID: PMC11226838.
20. Dickerson SM, Core AC. Estrogenic environmental endocrine-disrupting chemical effects on reproductive neuroendocrine function and dysfunction across the life cycle. Rev Endocr Metab Disord. 2007 Jun; 8(2): 143-59.
21. Cooper RL, Stoker TE, Tyrey L. Atrazine disrupts the hypothalamic control of pituitary-ovarian function. Toxicol Sci. 2000 Fe; 53 (2): 297–307
22. Rothman MS, Wierman ME. Female hypogonadism: evaluation of the hypothalamic-pituitary-ovarian axis. Pituitary. 2008; 11 (2): 163-9.
23. Messinis IE. Ovarian feedback, mechanism of action and possible clinical implications. Hum Reprod Update. 2006 Sep-Oct; 12 (5): 557-71.
24. Chrousos GP, Torpy DJ, Gold PW. Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications. Ann Intern Med. 1998 Aug 1: 129 (3): 229-40.