Dr. Mitra Basu Chhillar, M.D., M.B.A., F.A.M.

Medical Director, Soma Wellness Clinic

Introduction

Progesterone, a key hormone in both females and males, is often overlooked in clinical practice despite its profound systemic influence. With increasing recognition of hormonal imbalances contributing to widespread health issues such as insomnia, mood disorders, weight gain, and estrogen dominance, the use of bioidentical progesterone—especially via transdermal delivery—has emerged as a safe, effective, and well-tolerated intervention. This blog aims to educate medical doctors on the clinical application, rationale, biochemistry, indications, and administration of bioidentical progesterone in oil form, focusing on transdermal delivery.

Understanding Progesterone: Biochemistry and Functions

Progesterone is a steroid hormone synthesized primarily from pregnenolone, a derivative of cholesterol. In premenopausal women, it is mainly produced by the corpus luteum after ovulation, with additional synthesis by the adrenal glands and, in smaller amounts, peripheral tissues. In males and postmenopausal women, adrenal and peripheral conversion become the major sources.

Progesterone is not just a reproductive hormone. It acts as:

• A natural anxiolytic through its metabolites (e.g., allopregnanolone) acting on GABA-A receptors.
• A diuretic via antagonism of aldosterone.
• A modulator of neuroinflammation.
• A key player in immune balance, favoring Th2 dominance and reducing autoimmune flares.
• A balancer of estrogen, opposing estrogen-driven proliferation.
• 

Indications for Bioidentical Progesterone

Clinical use of bioidentical progesterone spans across multiple conditions:

1. Postmenopausal Women: To reduce hot flashes, correct insomnia, reverse vaginal atrophy, and provide protection against unopposed estrogen when on HRT.
2. Premenstrual Syndrome (PMS): For relief from bloating, mood swings, breast tenderness, and insomnia due to luteal phase deficiency.
3. Perimenopause: To address cycle irregularity, estrogen dominance, and anxiety.
4. Males with Low Progesterone: For men with symptoms of estrogen dominance (gynecomastia, weight gain, irritability), progesterone can offer balance and neuroprotection.
5. Other Indications:
   • Insomnia and early morning wakefulness
   • Anxiety and restlessness
   • Menstrual irregularities
   • Polycystic Ovarian Syndrome (PCOS)
   • Endometriosis
   • Osteoporosis (as progesterone promotes osteoblast activity)
   • Weight gain resistant to diet
   • Autoimmune disorders due to progesterone’s immunomodulatory role
   • Special note for Progesterone in males
   • Even though progesterone is often considered a “female” hormone, it plays critical roles in males, including:
   • Counteracting estrogen (it is a natural aromatase inhibitor)
   • Supporting GABAergic tone for calmness and sleep
   • Protecting the brain (neurosteroid function)
   • Regulating dihydrotestosterone (DHT) to prevent prostate hyperplasia
   • Balancing cortisol and other adrenal hormones

Why Transdermal Delivery?

Transdermal bioidentical progesterone offers several advantages:

• Bypasses hepatic first-pass metabolism, increasing bioavailability.
• Provides stable absorption when applied consistently.
• Has fewer gastrointestinal side effects compared to oral progesterone.
• Better compliance due to ease of use.

Limitations of Serum Progesterone Testing

It is critical to understand that serum progesterone often fails to reflect intracellular activity and clinical efficacy. Progesterone is a fat-soluble hormone that partitions into tissues. Studies have demonstrated that serum levels may remain deceptively low even after effective symptom resolution.

Instead, salivary progesterone or symptom tracking offers more reliable correlation with tissue saturation. Transdermal progesterone significantly raises salivary progesterone levels, showing effective tissue delivery.

Recommended Testing Protocol

• In Premenopausal Women: Serum progesterone tested on Day 21 or 22 of the menstrual cycle, ideally fasting. in males normal levels are 0.5 to 1.0 ng/mL
• In Postmenopausal Women or Males: Testing may be done any time in a fasted state.

A level below 10–12 ng/mL in symptomatic females is considered suboptimal.

Dosing and Administration Protocol

The protocol used in clinical practice is:

• Form: Natural bioidentical progesterone in oil (15 mg per 10 drops).
• Applicator: Dropper bottle for accurate dosing.
• Instructions:
  • Day 12 to Day 26 of the menstrual cycle: 8–12 drops nightly, applied on the forearm and rubbed with the opposite forearm just before sleep.
  • Day 1 to Day 12: 1–2 drops only.
  • Postmenopausal Women: Use continuously for 25–26 days per month, with a 4–5 day break.
  • Males: 2–4 drops every night before sleep, with adjustments based on symptoms.
• Bottle Advisory: Shake before each use.

Symptom Resolution as a Guide

Due to limitations in serum monitoring, the resolution of symptoms—improved sleep, reduction in bloating, emotional balance, reduction in breast tenderness and better cycle regularity—becomes the most reliable indicator of adequate tissue levels.

Safety and Side Effects

Bioidentical progesterone is remarkably safe:

• It does not convert to harmful metabolites unlike synthetic progestins.
• Rare side effects (if any) include grogginess, headache, or breast sensitivity at high doses.
• Easily reversed by dose reduction.

Mechanisms of Action

• Neurosteroid Effects: Metabolized in the brain to allopregnanolone, enhancing GABAergic inhibition (anti-anxiety, sleep-inducing).
• Estrogen Receptor Modulation: Reduces ER-alpha expression, controls estrogenic overstimulation.
• Anti-Inflammatory: Downregulates IL-6 and TNF-alpha.
• Bone Health: Promotes osteoblastogenesis via activation of progesterone receptors in bone.
• Metabolic: Improves insulin sensitivity and adipose tissue function.

Clinical Pearls

1. Symptomatology must guide treatment—not just labs.
2. Always start with a lower dose and titrate up.
3. Educate patients about cyclical use and its role in mimicking natural physiology.
4. Avoid using oral synthetic progestins in any circumstance unless specifically indicated.
5. Combine with lifestyle, micronutrient support (magnesium, vitamin B6, zinc), and phytoestrogens in estrogen-dominant women.
6. In PCOS or estrogen excess, always correct insulin resistance simultaneously.

Summary

Bioidentical transdermal progesterone is a cornerstone of hormone restoration therapy. It offers multifaceted benefits in women and men across age groups—from improving sleep, mood, weight, and metabolic health, to balancing excess estrogen, regulating menstrual cycles, and protecting against degenerative diseases. Given its low side effect profile, ease of use, and wide-ranging therapeutic applications, it is an indispensable tool in functional and regenerative medical practice.

References

1. Zava DT, Zava D. “Salivary hormone testing: Scientific basis and clinical utility.” Altern Ther Health Med. 2011.
2. Holtorf K. “The bioidentical hormone debate: Are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy?” Postgrad Med. 2009.
3. Prior JC. “Progesterone for symptomatic perimenopause treatment.” J Obstet Gynaecol Can. 2015.
4. Rapkin AJ, Mikacich JA, Moatakef-Imani B. “Progesterone treatment of premenstrual syndrome.” Int J Womens Health. 2019.
5. Genazzani AR, et al. “Progesterone, brain and behavior.” Gynecol Endocrinol. 2010.