What Is Progesterone? Other Names: Corpus Luteum Hormone, Luteohormone, Pregnanedione

What is Progesterone?

This post was written with Consensus AI Academic Search Engine – please read our Disclaimer at the end of this article. Progesterone is a crucial hormone in the human body, particularly in the context of reproductive health. It plays a significant role in regulating the menstrual cycle, maintaining pregnancy, and supporting various other physiological functions. Other names include: Bioidentical Progesterone, Corpus Luteum Hormone, Hormone de Grossesse, Hormone du Corps Jaune, Hormone Lutéale, Hormone Progestative, Luteal Hormone, Luteohormone, Lutine, Natural Progesterone, NSC-9704, Pregnancy Hormone, Pregnanedione, Prégnanedione, Progestational Hormone, Progesterona, Progestérone, Progesterone USP, Progesteronum, 4-Pregnene-3; 20-Dione.

Role in Pregnancy

Progesterone is essential for maintaining a healthy pregnancy. It prepares the endometrium for implantation of the fertilized egg and helps maintain the uterine lining throughout pregnancy. Studies have shown that progesterone supplementation can be beneficial in certain high-risk pregnancy scenarios. For instance, vaginal progesterone has been used to reduce the risk of preterm birth in women with a history of spontaneous preterm birth or other risk factors1 2. However, the effectiveness of progesterone in preventing preterm birth in twin pregnancies remains inconclusive6 10.

Progesterone and Miscarriage

Progesterone therapy has been investigated for its potential to prevent miscarriages, particularly in women with a history of recurrent miscarriages. The PROMISE trial, for example, found no significant difference in live birth rates between women who received progesterone and those who received a placebo3 4. Similarly, the PRISM trial explored the use of progesterone in women with early pregnancy bleeding and found that while there was no overall significant increase in live birth rates, certain subgroups did benefit from the treatment8.

Neuroprotective Effects

Beyond its role in reproductive health, progesterone has also been studied for its neuroprotective properties. Research indicates that progesterone may have beneficial effects in the context of traumatic brain injury. A pilot clinical trial suggested that progesterone administration could reduce mortality rates and improve outcomes in patients with moderate traumatic brain injury5.

Progesterone and Sleep

Progesterone has been found to influence sleep patterns, particularly in postmenopausal women. A study demonstrated that progesterone administration could reduce sleep disturbances and improve sleep quality by increasing slow-wave sleep and reducing wakefulness after sleep onset7.

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Uses of Progesterone

Sleep Regulation

Progesterone can help improve sleep quality, particularly in postmenopausal women. It has been shown to reduce sleep disturbances and increase the duration and intensity of deep sleep, acting as a physiological regulator rather than a hypnotic drug1.

Stress and Anxiety Reduction

Progesterone has been found to reduce stress-induced symptoms such as craving, anxiety, fear, anger, and sadness in individuals with alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD). It also improves cognitive performance under stress2.

Prevention of Preterm Birth

Progesterone is widely used to prevent preterm birth in high-risk pregnancies. However, its effectiveness varies:

Vaginal Progesterone: Some studies show it reduces the rate of preterm birth in high-risk singleton pregnancies9, while others found no significant effect in twin pregnancies3 or in broader high-risk groups8.

Oral Micronized Progesterone: Its role in preventing recurrent spontaneous preterm delivery is still under investigation5.

Luteal Phase Support in Assisted Reproduction

Progesterone is used for luteal phase support in assisted reproduction cycles, such as IVF. Both vaginal capsules and gel forms are effective, with similar pregnancy rates observed6.

Contraceptive Use

Progesterone-based contraceptives not only prevent pregnancy but also modulate immune responses. They can reduce morbidity during primary influenza infections but may increase susceptibility to secondary infections due to their immunomodulatory effects4.

Nicotine Withdrawal Management

Progesterone has sex-dependent effects on nicotine withdrawal. In males, it may worsen withdrawal symptoms and anxiety during abstinence, while in females, it can make nicotine’s effects feel stronger7.

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Adverse Effects of Progesterone

Physical Adverse Effects

Breast Tenderness: Progesterone, especially when combined with estrogen, can cause breast tenderness. This effect was noted in postmenopausal women undergoing hormone replacement therapy2 3.

Vaginal or Genital Discharge and Irritation: Women on estrogen plus progestin therapy reported increased vaginal or genital discharge and irritation compared to those on placebo3.

Headaches: An increase in headaches was observed in women receiving estrogen plus progestin therapy3.

Vaginal Bleeding: Progesterone treatment can lead to vaginal bleeding, which was significantly higher in women on combined estrogen and progestin therapy compared to placebo3.

Gynecologic Surgeries: There was an increased rate of gynecologic surgeries, such as hysterectomy and dilation and curettage, in women receiving combined hormone therapy3.

Mental and Emotional Effects

Mood Changes: Some studies have shown that progesterone can cause mood changes, including increased sensitivity and aggression, although these effects were not statistically significant in all cases1 5.

Anxiety and Nicotine Withdrawal: In male smokers, progesterone increased nicotine withdrawal symptoms and anxiety during brief abstinence periods9.

Cardiovascular and Thrombotic Effects

No Significant Impact on Vascular Function: Progesterone alone did not adversely affect vascular function in postmenopausal women, indicating it does not significantly alter blood pressure, systemic arterial compliance, or other vascular parameters10.

No Increase in Thrombotic Factors: Topical progesterone cream did not increase thrombotic and inflammatory factors in postmenopausal women, suggesting it may be a safer alternative to conventional hormone replacement therapy4.

Other Effects

Sedative-like Effects: Progesterone and its metabolites can produce mild sedative-like effects, such as decreased vigor and increased feelings of sluggishness, particularly at higher doses5.

No Significant Mental Health Effects in ART: Progesterone supplementation in women undergoing assisted reproductive treatment did not cause significant mental health adverse effects compared to a control group1.

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How has Progesterone Improved Patient Outcomes?

Traumatic Brain Injury (TBI)

Improved Neurologic Outcomes: Progesterone administration in patients with acute severe TBI has shown improved neurologic outcomes at 3 and 6 months, as measured by the Glasgow Outcome Scale and the modified Functional Independence Measure scores. Additionally, the mortality rate was significantly lower in the progesterone group compared to the placebo group1 6.

Reduction in Inflammatory Markers: In patients with diffuse axonal injury (DAI), progesterone improved outcomes by reducing serum levels of inflammatory markers (IL-1β, MDA, S-100B) and increasing levels of IL-6 and TGF-β14 8.

Mixed Results in Larger Trials: A larger multicenter trial did not find significant differences in outcomes between progesterone and placebo groups, suggesting that while some smaller studies show promise, larger trials have not consistently confirmed these benefits3.

Breast Cancer

Node-Positive Breast Cancer: A single preoperative injection of hydroxyprogesterone showed significant improvement in disease-free survival (DFS) and overall survival (OS) in node-positive breast cancer patients. However, no significant benefit was observed in the overall population of operable breast cancer patients2.

COVID-19

Improved Clinical Outcomes: In a pilot study, adding progesterone to the standard of care for hospitalized men with moderate to severe COVID-19 resulted in improved clinical status, reduced need for supplemental oxygen, and shorter hospital stays5.

Preterm Birth

No Significant Benefit: Progesterone prophylaxis to prevent preterm birth did not show significant benefits in obstetric, neonatal, or childhood outcomes. The studies concluded that progesterone had no significant effect on reducing preterm birth or improving long-term outcomes for children9 10.

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Progesterone Mechanisms of Action

Regulation of Gene Expression

Progesterone acts by binding to progesterone receptors (PR) in target cells, which then interact with DNA to regulate the expression of specific genes. This regulation is essential for preparing the endometrium for pregnancy by inducing the expression of transforming growth factor (TGF-β2), which helps down-regulate matrix metalloproteinases (MMPs) and maintain an appropriate endometrial environment1.

Immune Modulation

Progesterone promotes immunosuppression in the mammary gland by increasing the number and activity of regulatory T cells (Tregs). This immunosuppressive environment can facilitate tumor growth in hormone-receptor-positive breast cancer by decreasing the activity of anti-tumor CD8+ T cells2.

Antigonadotropic Activity

Progesterone and its derivatives, such as norethisterone acetate (NETA) and nomegestrol acetate (NOMA), exhibit antigonadotropic activity by decreasing the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This effect is not mediated through the androgen receptor but likely involves direct action on the pituitary gland3.

Sleep Regulation

Progesterone has been shown to prevent sleep disturbances and improve sleep architecture by reducing wakefulness after sleep onset and increasing slow-wave sleep. This effect is thought to be mediated by neuroactive metabolites of progesterone that produce sedative-like effects4 6.

Direct Pituitary Action

Progesterone can stimulate LH secretion by acting directly on the pituitary gland. This action is evident in women with hypothalamic gonadotropin deficiency, where progesterone treatment increases LH pulse amplitude and overall LH levels5.

Ovulation Inhibition

Progesterone and its analogs can inhibit ovulation through different mechanisms. For example, RU486, an antiprogesterone, inhibits ovulation by acting at the hypothalamic level, interfering with steroidal feedback signals from the ovary. In contrast, levonorgestrel (LNG) inhibits ovulation by direct progesterone-like effects on folliculogenesis and the hypothalamus8.

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Common Complaints Associated with Progesterone Use

Mood-Related Complaints

Irritability and Mood Swings: Users of oral progestins often report irritability and mood swings, which can be significant enough to lead to discontinuation of hormone replacement therapy (HRT)3.

Anxiety and Tension: In male smokers, progesterone has been shown to increase anxiety and tension during nicotine withdrawal periods2.

Physical Complaints

Bloating and Headaches: Bloating and headaches are common side effects experienced by users of oral progestins3.

Gender-Specific Effects

Increased Nicotine Withdrawal in Males: Progesterone can worsen nicotine withdrawal symptoms in males, making it harder for them to quit smoking2.

Limited Effects in Females: In contrast, females did not experience significant negative effects from progesterone in the context of nicotine withdrawal2.

Sleep Disturbances

Sleep Modulation: While progesterone can help reduce sleep disturbances and improve sleep quality in postmenopausal women, it does not affect undisturbed sleep4.

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