Hormonal Imbalance and Premenstrual Syndrome (PMS)

In women, the most pronounced cyclical changes occur in the endometrium and constitute the uterine (menstrual) cycle. Cyclical processes within the ovaries are closely associated with steroidogenesis—the production of sex steroid hormones. Cholesterol serves as the precursor for all steroid hormones. Estradiol is synthesized throughout the reproductive years, while progesterone prepares the body for conception and supports pregnancy. An imbalance in progesterone levels is one of the common contributors to premenstrual syndrome (PMS).

Estrogen Imbalance

Hyperestrogenism

Hyperestrogenism is a hormonal disorder characterized by elevated estrogen levels. It may develop in association with conditions such as polycystic ovary syndrome (PCOS) or hypothyroidism, both of which can increase estrogen production. Obesity is another contributing factor, as excess adipose tissue converts androgens into estrogens through a process known as aromatization. Liver dysfunction can also play an important role because the liver is responsible for metabolizing estrogens and eliminating their excess from the body.

Common manifestations of hyperestrogenism include menstrual irregularities, such as heavy, prolonged, or irregular menstrual bleeding, as well as spotting or bleeding between periods. Other symptoms may include breast tenderness, weight gain, mood swings, and changes in sexual desire ranging from markedly reduced libido to increased sexual drive.

Hypoestrogenism

Hypoestrogenism is a hormonal disorder caused by estrogen deficiency. It may result from impaired function of the hypothalamic-pituitary axis, ovarian dysfunction, or various external factors.

The earliest and most common consequence of declining estrogen levels is disruption of the menstrual cycle, including light or short menstrual periods, prolonged intervals between cycles, or complete cessation of menstruation (amenorrhea). Persistent estrogen deficiency may also contribute to infertility due to impaired ovulation.

Common Symptoms of Female Hormonal Imbalance

Menstrual cycle

• Irregular menstrual periods
• Excessively heavy or unusually light menstrual flow
• Severe menstrual pain

Psychological symptoms

• Persistent irritability
• Apathy
• Panic attacks
• Increased emotional sensitivity and tearfulness, particularly during the 7–10 days preceding menstruation

Physical appearance

• Adult acne, especially around the chin and jawline
• Excessive hair loss or, conversely, unwanted hair growth on the face, chest, or other areas

Weight

• Difficulty losing weight despite diet and exercise
• Rapid weight gain, particularly around the abdominal area

General well-being

• Chronic fatigue
• Insomnia
• Decreased libido

Major Causes of Female Hormonal Imbalance

Chronic stress. Elevated cortisol production may divert pregnenolone—the common precursor for steroid hormone synthesis—away from progesterone production, a phenomenon commonly referred to as the “pregnenolone steal.”

Sleep disturbances. Melatonin plays an essential role in regulating hormonal rhythms, and inadequate sleep may disrupt endocrine balance.

Nutrition. Deficiencies in dietary fats (cholesterol is required for steroid hormone synthesis), inadequate protein intake, and restrictive dieting may impair hormone production.

Insulin resistance. Persistently elevated blood glucose levels can disrupt ovarian function and are a common contributing factor to polycystic ovary syndrome (PCOS).

Endocrine disruptors (xenoestrogens). Chemicals found in plastics, household products, and cosmetics can mimic the biological activity of estrogen, contributing to estrogen excess.

Premenstrual Syndrome (PMS)

According to the International Classification of Diseases, 10th Revision (ICD-10), premenstrual syndrome is classified under code N94.3 — Premenstrual Tension Syndrome. It belongs to the category of non-inflammatory disorders of the female genital tract.

Premenstrual syndrome affects approximately 20–30% of women, with 5–10% experiencing severe symptoms. PMS is most commonly observed in women between 30 and 40 years of age, while its manifestations generally become less pronounced during the early menopausal transition.

PMS is a recurrent disorder (from the Latin recurrens, meaning “returning”) that occurs during the luteal phase of the menstrual cycle for at least two to three consecutive cycles. Its symptoms diminish or resolve shortly after the onset of menstruation.

PMS is characterized by somatic (physical), psycho-emotional, cognitive, and behavioral (affective) symptoms that negatively affect a woman’s quality of life and social functioning.

The menstrual cycle consists of three phases: the follicular, ovulatory, and luteal phases.

During the follicular phase, estrogen and progesterone levels are low. As a result, the thickened inner lining of the uterus (the endometrium) is shed, initiating menstruation. Subsequently, the level of follicle-stimulating hormone (FSH) gradually increases, stimulating the maturation of ovarian follicles that contain the oocytes. At the same time, estrogen production begins to rise.

The ovulatory phase begins with the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) into the bloodstream. LH triggers ovulation by stimulating the release of a mature egg from the ovary. Following ovulation, estrogen levels decline while progesterone production begins to increase.

During the luteal phase, LH and FSH levels decrease, and the corpus luteum forms, producing progesterone. Estrogen levels remain relatively high throughout this phase. If fertilization does not occur, the corpus luteum degenerates, estrogen and progesterone levels decline, and menstruation begins.

It is believed that PMS symptoms are associated with estrogen dominance and result from an exaggerated response of the central nervous system, as well as other organs and body systems, to the normal hormonal fluctuations that occur throughout the menstrual cycle.

During the menstrual cycle, fluctuations in estrogen levels influence the concentration of the neurotransmitter serotonin. Reduced serotonin levels are associated with common PMS symptoms, including insomnia, fatigue, and depressed mood.

Following ovulation, progesterone becomes the dominant hormone during the second half of the cycle. It exerts calming and sedative effects on the nervous system. While estrogen may be considered an “activating hormone,” progesterone functions as a “stabilizing hormone.” However, the rapid decline of both hormones immediately before menstruation is believed to trigger the cluster of symptoms collectively known as Premenstrual Syndrome (PMS).

Depending on the predominant clinical manifestations, PMS is commonly classified into four clinical forms:

• Neuropsychological form: irritability, anxiety, aggression, and depression.
• Edematous form: fluid retention, mastalgia (breast pain), breast swelling, abdominal bloating, and weight gain.
• Cephalgic form: migraine-like headaches.
• Crisis form: episodes resembling sympathoadrenal crises, typically occurring before menstruation.

Mild manifestations of PMS, such as slight irritability, increased tearfulness, or cravings for specific foods, are experienced by approximately 90% of women.

However, 3–5% of women develop Premenstrual Dysphoric Disorder (PMDD), a severe condition whose symptoms can profoundly disrupt daily functioning.

Dysphoria is a state characterized by intense inner tension, persistent dissatisfaction with oneself and the surrounding world, and an increased tendency to respond to minor events with sudden, often aggressive emotional reactions. The term originates from the Greek word dysphoria, meaning “a difficult state” or “discontent.”

Premenstrual Dysphoric Disorder (PMDD) is the most severe form of PMS. It is not simply “very severe PMS” but a distinct medical condition officially recognized in international diagnostic classifications.

PMDD symptoms occur cyclically during the luteal phase of the menstrual cycle (approximately 5–11 days before menstruation) and substantially improve or completely resolve within the first few days of menstrual bleeding. Nevertheless, these symptoms can significantly interfere with work, education, interpersonal relationships, and overall daily functioning.

The prevalence of PMDD is estimated at 5–8%, with the highest rates observed among women aged 16–19 years and 25–34 years.

The pathophysiology of depressive symptoms in PMDD is believed to involve an imbalance of several neurotransmitters, including serotonin, norepinephrine, dopamine, acetylcholine, gamma-aminobutyric acid (GABA), and glutamate. Another proposed mechanism is reduced neuroplasticity, referring to the brain’s diminished ability to adapt its structure and function in response to new experiences and environmental demands.

Symptoms of Premenstrual Dysphoric Disorder (PMDD)

PMDD is characterized by profound sadness, feelings of hopelessness that may progress to suicidal ideation, severe anxiety, persistent inner tension, a sense of being “on the verge of losing control,” marked mood swings, sudden crying spells, loss of interest in usual activities and social interactions, and a feeling of losing control over one’s emotions and behavior.

Pathophysiological Mechanisms and Clinical Manifestations of PMDD

* Allopregnanolone is a neuroactive metabolite of progesterone that acts as a potent positive modulator of GABA-A receptors. In women with PMS, the adaptive response to cyclical fluctuations in allopregnanolone levels is impaired, particularly during its decline in the late luteal phase, contributing to the development of anxiety and depressive symptoms.
** GABA (gamma-aminobutyric acid) is one of the brain’s primary inhibitory neurotransmitters. Its principal function is to reduce neuronal excitability and promote relaxation of the nervous system.

Only calcium has been consistently supported by clinical research and endorsed by professional medical societies as an effective micronutrient for PMS management. Calcium supplementation at a dose of 1,000–1,200 mg/day has been shown to significantly reduce the severity of somatic PMS symptoms, including mastalgia, edema, and headaches. It may be used as monotherapy for mild PMS or as part of a comprehensive treatment strategy.

VedaPulse for PMS Assessment and Personalized Management

In women with Premenstrual Syndrome (PMS), as well as PMS accompanied by other conditions (such as migraine), heart rate variability (HRV) frequently changes. Hormonal fluctuations occurring before menstruation—particularly the decline in estrogen and progesterone levels—may exacerbate autonomic nervous system imbalance.

One of the most common findings is a reduction in overall HRV, reflected by a decreased SDNN value. This indicates reduced cardiac autonomic flexibility, meaning the body becomes less capable of adapting to physical or emotional stress.

At the same time, sympathetic nervous system activity often increases. During the premenstrual phase, the Stress Index (SI)—an indicator of regulatory system tension—typically rises. The Mode Amplitude (AMo) may also increase, serving as another marker of sympathetic predominance.

Changes in autonomic balance may also be reflected by an elevated LF/HF ratio, indicating increased sympathetic activity and/or reduced parasympathetic activity. In some women, the contribution of the parasympathetic (vagal) component, which is usually more pronounced during other phases of the menstrual cycle, becomes diminished.

HRV assessment therefore provides valuable insight into whether the body’s adaptive mechanisms are under excessive strain and require clinical attention.

Electrolyte Balance

During the luteal phase of the menstrual cycle, progesterone influences potassium and magnesium metabolism. Deficiencies of these electrolytes may independently impair cardiac function and contribute to a reduction in heart rate variability (HRV).

Hydration

Dehydration places additional strain on the cardiovascular system and may contribute to reduced heart rate variability (HRV).

During the premenstrual period, some women experience a shift toward sympathetic nervous system predominance—the body’s “stress mode,” characterized by an increased heart rate and mobilization of physiological resources. This shift may be accompanied by an increase in the Stress Index (SI), indicating that the body’s adaptive regulatory mechanisms are functioning under increased strain.

At the same time, overall HRV may decrease, as reflected by a lower SDNN value. This phenomenon is thought to be associated with the increased anxiety and occasional cardiac discomfort commonly experienced during PMS, both of which reflect heightened autonomic nervous system tension.

It is also important to consider the individual’s baseline autonomic regulation pattern. Women with vagotonia (predominant parasympathetic activity) generally do not exhibit significant heart rhythm disturbances or marked adaptive stress throughout the menstrual cycle. In contrast, women with sympathicotonia (predominant sympathetic activity) often demonstrate more pronounced premenstrual changes, including increased tachycardia and greater suppression of autonomic regulatory activity.

Clinical Case

Patient: Female, 43 years old; height 167 cm; weight 70 kg.

Chief complaints: Low energy, difficulty waking up in the morning, chronic stress accompanied by emotional eating, autoimmune thyroiditis (AIT), hypothyroidism, TSH 2.7 mIU/L, overweight, edema, small uterine fibroid, fibrocystic breast disease (FBD), gallbladder flexure, and increased vascular fragility.

Biohacking Module Assessment

Reproductive System

• Overall Status: 51.48 a.u. (High Risk)
• Hormonal Balance: 60.42 a.u. (High Risk)
• Ovaries: 45.93 a.u. (Moderate Risk)
• Uterus: 56.29 a.u. (High Risk)

Endocrine System

• Overall Status: 47.94 a.u. (Moderate Risk)
• Insulin Resistance: 41.69 a.u. (Moderate Risk)
• Adrenal Function: 100.00 a.u. (Very High Risk)
• Lipid Metabolism: 38.27 a.u. (Moderate Risk)
• Calcium Metabolism: 51.96 a.u. (High Risk)

Neuropsychological Disorders

• Overall Status: 56.17 a.u. (High Risk)
• Memory Impairment: 57.44 a.u. (High Risk)
• Cognitive Dysfunction: 61.47 a.u. (High Risk)
• Emotional Disorders: 59.93 a.u. (High Risk)
• Psychophysiology — Emotional Lability: 6.7 a.u.

What Comes Next?

The next step is to use the Phyto Encyclopedia, Aroma Encyclopedia, Nutraceuticals, and Diet modules to develop a comprehensive, personalized program for the prevention and management of PMS and PMDD, tailored to the patient’s individual functional health profile.