First Progesterone

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Medically reviewed

Laura Arias

Last updated on 22/12/2025

This page provides general, reference-level information compiled from official medical sources. It is not a substitute for professional medical advice, diagnosis, or treatment. For decisions about your health, please consult a qualified healthcare professional.

Overview of First Progesterone

Property Description
Active Ingredient (INN) Progesterone
Brand Name First Progesterone VGS (VGS 100, VGS 200, etc.)
Pharmacological Class Progestin/Progestogen
Dosage Form Vaginal Suppository/Compounding Kit
Rx Status Prescription Only (Rx)

First Progesterone VGS is a brand-specific, prescription-only (Rx) medication that contains the hormone progesterone as its active ingredient, classifying it within the progestin pharmacological class. This particular product is differentiated by its specialized vaginal suppository dosage form, which is designed to ensure efficient, local delivery of the hormone.

This form of administration is often clinically recognized for optimizing drug absorption when precise hormonal delivery is needed, such as in certain fertility and hormonal replacement contexts. The product is manufactured by Cutis Pharma Inc. (Amneal) and is a specialty medication used to provide targeted hormonal support.


Composition and Therapeutic Purpose

The progesterone in First Progesterone VGS is micronized, naturally-derived progesterone, meaning it is chemically bioidentical to the hormone produced by the human body. This substance is synthesized in a lab from plant-based materials and is then micronized—a process that reduces particle size to enhance the speed and consistency of absorption.

The overarching therapeutic purpose of this medication is to correct conditions stemming from a progesterone deficiency or the need for consistent supplementary hormonal levels. Its role is centered on providing foundational hormonal support to help regulate reproductive and endocrine functions. A healthcare provider determines the specific need for this type of hormonal replacement.

What side effects are possible with First Progesterone?

Possible Side Effects and Safety Information

The official safety profile for Progesterone vaginal suppositories (First Progesterone VGS) is derived from regulatory classifications that document adverse reactions and safety constraints.


Adverse Reaction Scope

Adverse effects are categorized by the physiological system affected and their reported incidence in clinical trials.

Category Description based on Regulatory Sources
Frequency classification Effects are classified by incidence rates. Very Common (ge 10%) includes Post-oocyte retrieval pain (in ART settings). Common (ge 1% to 10%) effects involve Abdominal pain, Nausea, Headache, and Ovarian hyperstimulation syndrome (OHSS).
System-organ classes involved Effects are grouped across systems including Reproductive System and Breast Disorders, Gastrointestinal Disorders, Nervous System Disorders, and local Administration Site Conditions (e.g., Vaginal irritation).

Serious Adverse Reactions and Restrictions

The label identifies serious risks associated with the progestogen class, which require defined safety constraints for use.

  • Serious Adverse Reactions: Risks of Arterial and Venous Thromboembolic Disorders (including Deep Vein Thrombosis and Pulmonary Embolism) and risks related to severe Hepatic Impairment or known/suspected Malignancy of the breast are documented.
  • Safety-Related Restrictions: The medicine is contraindicated in individuals with a history of thromboembolic events, severe liver disease, or undiagnosed abnormal vaginal bleeding.
  • Population-Specific Safety: Patients with a history of depression must be observed closely for worsening symptoms, with discontinuation considered if symptoms significantly worsen.

This structure ensures the safety profile is clearly communicated, establishing the boundaries of appropriate use as defined by official regulatory bodies.

Overdose and Emergency Response

Overdose and When to Seek Help

Regulatory documentation for Progesterone establishes the official profile for situations involving excessive exposure. Overdose manifestations are primarily linked to transient central nervous system effects. Officially documented signs may include somnolence, drowsiness, and transient dizziness. Other manifestations reported in regulatory sources involve the gastrointestinal system, such as nausea and vomiting, in addition to symptoms like headache and fatigue.

Immediate Medical Attention Required

While overdose is often described in regulatory sources as potentially self-limiting, seek immediate medical attention for any known or suspected excessive exposure. Urgent contact with emergency services or a Poison Control Center is specifically mandated if severe signs are observed, such as severe neurological impairment (e.g., passing out, inability to arouse) or acute breathing difficulties. The determination for hospitalization is based on the severity of the observed clinical signs.

Official Management and Antidote Status

The official procedural guidance for managing an overdose is the immediate discontinuation of the medication. Treatment is strictly symptomatic and supportive. Regulatory documents confirm that no specific antidote is known to pharmacologically reverse the effects of Progesterone overdose. Clinical observation is generally required to monitor the resolution of the transient effects.

Therapeutic Uses of First Progesterone

What First Progesterone Treats: Main Uses and Benefits

Progesterone vaginal suppository (First Progesterone) is commonly used to help manage symptoms and conditions related to hormonal deficiency in reproductive health. The use is relevant in clinical settings marked by temporary physiological imbalance.

The medication is applied across domains where additional symptomatic support is needed in fertility treatments, such as Assisted Reproductive Technology (ART) procedures like In Vitro Fertilization (IVF) and Frozen Embryo Transfer (FET). The primary benefit supports the establishment of a stable uterine environment, which may assist with supporting patients during difficult symptomatic phases in infertile women.

First Progesterone is also relevant in clinical settings that involve acute or unstable symptom patterns, such as high-risk pregnancies marked by a history of spontaneous preterm birth or findings like a short cervix. This use is commonly applied when appropriate to help with managing symptoms related to heightened physiological stress and supports the patient during episodes of heightened discomfort. Furthermore, for non-pregnant women, it assists with re-establishing a predictable menstrual cycle in cases of secondary amenorrhea through supportive symptomatic management.


Quick Fact: Relief for Hormonal Deficiency Symptoms This medication is commonly used to help manage symptoms that create noticeable physiological strain and is relevant across conditions presenting with systemic or localized discomfort.

Regulatory References

  1. NIH MedlinePlus overview

Eligibility and Restrictions for Use

The eligibility for using progesterone vaginal suppositories, such as First Progesterone VGS, is strictly defined by regulatory guidelines, focusing on pre-existing conditions and population demographics.

Populations Who Must Not Use the Medicine (Contraindications)

Official prescribing information prohibits the use of this medicine in women with the following documented conditions:

  • Known sensitivity or allergy to progesterone or any component of the suppository.
  • A history of or current arterial or venous thromboembolism (blood clots) or severe thrombophlebitis.
  • Severe hepatic impairment or disease (severe liver disease).
  • Known or suspected malignancy of the breast or genital organs.
  • Undiagnosed vaginal bleeding.
  • Known missed abortion or ectopic pregnancy.

Age and Physiological Restrictions

Category Eligibility Rule (Official Documentation)
Standard Use Approved for use in infertile women undergoing Assisted Reproductive Technology (ART) procedures.
Pediatric Use Not intended for use in children under 18; safety and effectiveness not established
Geriatric Use Not intended for women 65 years of age and older.
Pregnancy Use is restricted to specific labeled indications (e.g., luteal phase support during ART).
Lactation Not recommended due to progesterone passing into breast milk.

These rules ensure the medication is used exclusively within the specific adult populations and clinical contexts for which regulatory authorities have defined its use.

What should I know about interactions with other medicines?

First Progesterone Interactions with other medicines and products

The interaction profile for First Progesterone is primarily defined by its metabolic clearance through hepatic cytochrome P450 3A4 (CYP3A4).


Documented Interaction Categories and Constraints

Interaction Domain Mechanistic Basis in Official Labeling
Enzyme Inducers Increases the clearance of First Progesterone, leading to reduced plasma concentration of the drug.
Enzyme Inhibitors Decreases the clearance of First Progesterone, leading to increased plasma concentration of the drug.
Food/Beverage Concurrent use may increase systemic exposure of the product, necessitating specific administration conditions.

Specific Interacting Medicines and Substances

Interacting medicinal product categories explicitly listed in regulatory documents include strong CYP3A4 inducers (e.g., Carbamazepine, Phenytoin, Rifampicin, Barbiturates) and strong CYP3A4 inhibitors (e.g., Ketoconazole, Ritonavir, Clarithromycin). The use of the herbal product St. John's wort is also stated to reduce the concentration of the drug.

Interaction-related restrictions require caution or adjustment of the regimen when combining with these agents, as a reduction in drug exposure may affect therapeutic outcome, and increased exposure may elevate the potential for adverse effects. The official labeling may also state a constraint against taking the product with food to control its systemic absorption and exposure.

Mechanism of Action

Activation of Nuclear Progesterone Receptors

The drug acts as a specific agonist for intracellular progesterone receptors (PRs), causing the receptor complex to move into the cell nucleus. This complex binds to DNA, directly modulating gene expression to regulate the synthesis of proteins, initiating the molecular cascade that leads to the drug's effects.

Modulating Uterine Transformation and Function

This receptor activation drives the endometrial transformation, shifting the uterine lining from a growth state to a secretory state (decidualization). This mechanism results in a transformed uterine environment and decreases the excitability (quiescence) of the uterine muscle, which are key physiological changes resulting from the mechanism.

Central Endocrine Feedback Control

Progesterone also engages the neuroendocrine control system by exerting negative feedback on the Hypothalamic-Pituitary-Ovarian (HPO) axis. This action modulates the release of hormones like Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH), which affects the signaling sequence that governs the reproductive cycle's timing.

Dosage and Administration Information

Administration Guidelines for Progesterone

The following instructions define the proper use of micronized progesterone. The specific form and route of administration are defined by the prescribed regimen, which may involve oral, vaginal, or injectable use.

Administration Scope

Parameter Instruction
Route of Administration Oral (capsule), Vaginal (insert/gel), or Parenteral (IM/SC injection).
Dosing Schedule Varies by formulation and indication. Common doses include 200 mg orally once daily, or 90–100 mg vaginally one to three times daily.
Timing in Relation to Meals Oral capsules are often specified to be taken at bedtime, and sometimes without food, to optimize absorption or mitigate potential central nervous system effects.
Special Procedural Conditions Oral capsules must be swallowed whole and must not be chewed, crushed, or divided. Vaginal products should not be administered simultaneously with other vaginal preparations.

Procedural Rules

  • Missed Dose: If a dose is forgotten, the instruction is typically to take it as soon as it is remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped to maintain the correct daily frequency. Do not double the dose.
  • Course Duration: The length of therapy is explicitly defined in days or weeks, such as 10–12 consecutive weeks for luteal support, or 12 days per 28-day cycle for endometrial protection.

Connection to the Overall Use Protocol

These guidelines establish the structure for using the medicine by setting a precise administration route, dose strength, and frequency (e.g., 200 mg oral capsule once daily). Adherence to these parameters, including the requirement to swallow capsules whole and follow the defined course duration, ensures the product is used in accordance with established usage protocols.

Recent Clinical Evidence

Progesterone: Recent Clinical Evidence

Overview of Clinical Research

Clinical evidence regarding progesterone primarily focuses on its use in hormone replacement therapy and specific reproductive health applications. The majority of research consists of randomized, controlled trials (RCTs) and systematic reviews, which provide the most robust level of evidence for evaluating therapeutic outcomes.

Key Areas of Study

Research Focus Primary Outcome Measured
Endometrial Protection Prevention of endometrial hyperplasia in women receiving estrogen therapy.
Infertility/Assisted Reproduction Support of the luteal phase and rates of clinical pregnancy.
Recurrent Pregnancy Loss Live birth rates in women with a history of unexplained miscarriage.

Summary of Findings

Studies consistently show that progesterone administration is associated with the prevention of estrogen-related endometrial thickening in postmenopausal women. Research in assisted reproductive technologies (ART) has explored its role in optimizing conditions for embryo implantation.

The findings related to the prevention of miscarriage are subject to ongoing study. Evidence from recent large-scale trials has been reviewed, with specific attention given to the timing of administration and the patient population (e.g., women with documented prior losses vs. those with acute threatened miscarriage).

Safety and Tolerability

The most commonly reported adverse events in clinical trials include headache, breast tenderness, and mood changes. Due to its hormonal nature, specific attention in research is given to potential interactions with other hormonal agents and the monitoring of long-term risks, such as those related to cardiovascular health.

Key Studies & References

  1. The effects of progestogens on the endometrium in postmenopausal women receiving oestrogen therapy: a systematic review and meta-analysis of randomised trials
  2. Guideline: Management of recurrent miscarriage

Frequently Asked Questions (FAQ)

Common questions about First Progesterone (FAQ)


Q: What are the main differences between First Progesterone and synthetic progestins?

First Progesterone is described as a naturally-derived or bioidentical hormone, meaning its chemical structure is identical to the progesterone produced by the human body. Progestins, in contrast, are the synthetic, human-made compounds that are designed to mimic the effects of the natural hormone. While both belong to the same pharmacological class, their chemical compositions differ slightly.


Q: Does official information list weight gain as a frequent side effect of First Progesterone?

Official documentation lists 'change in weight (increase or decrease)' as a documented adverse reaction associated with progesterone treatment. Additionally, other common side effects, such as fluid retention or bloating, are often reported. These factors may contribute to perceived changes in weight during the course of therapy.


Q: Is it common to experience mood changes, anxiety, or depression while taking First Progesterone?

Official labeling indicates that mood swings and depression are expected adverse reactions. Official warnings indicate that individuals with a history of depression require close observation by a healthcare professional for any worsening of symptoms. Anxiety is sometimes reported but may fall under the general category of mood changes.


Q: What is the general information about the long-term safety of using First Progesterone?

Regulatory agencies require careful monitoring of the long-term use of hormone therapy for potential risks, including those related to cardiovascular health and certain cancers. Recent data reviews suggest that research is often focused on examining potential long-term benefits in relation to factors like bone loss when therapy is initiated earlier.


Q: Does First Progesterone affect the risk of developing breast cancer according to regulatory data?

Progesterone is contraindicated (prohibited) for individuals with a known or suspected malignancy of the breast or genital organs. Regulatory studies examining Hormone Replacement Therapy (HRT) have explored the risk of breast cancer diagnosis, which informs official warnings and monitoring protocols.


Q: How long does it usually take for the effects of First Progesterone to become noticeable?

The time it takes for the effects to become noticeable can vary based on the specific formulation (e.g., oral, vaginal) and the condition being treated. Pharmacokinetic data indicates that the body absorbs the active ingredient within hours. For some indications, clinical effects, such as withdrawal bleeding, may be observed within 48 to 72 hours after stopping a course of therapy.


Q: Why is First Progesterone sometimes prescribed to women who have had a hysterectomy?

Progesterone is primarily included in hormone therapy when a woman still has her uterus, as it protects the uterine lining from the risk of cancer associated with estrogen. For individuals who have had a hysterectomy (surgical removal of the uterus), this need for endometrial protection is generally eliminated, and progesterone is usually not required.


Q: What is the relationship between First Progesterone and sleep quality?

Progesterone is known to have a sedative effect because it interacts with certain receptors in the brain. Official administration guidelines for the oral form often specify taking it at bedtime. This timing is typically recommended due to the potential sedative effects, which may mitigate daytime drowsiness.


Q: Can First Progesterone be used to help manage symptoms of perimenopause?

Progesterone is a component of Hormone Replacement Therapy (HRT) that may be prescribed to address common menopausal symptoms such as hot flashes and night sweats. A healthcare provider determines if the use of First Progesterone is appropriate for managing specific perimenopausal symptoms.


Q: What is the difference between prescription First Progesterone and over-the-counter progesterone creams?

Prescription progesterone products are approved by regulatory agencies for specific medical uses, have established safety and efficacy profiles, and are manufactured to ensure precise dosing. Non-prescription (over-the-counter) creams are not subject to the same approval process and may contain varying amounts of progesterone, meaning their safety and efficacy are not reliably established.


Q: Are there restrictions on driving or operating machinery while using First Progesterone?

Yes, official product information includes warnings regarding activities that require alertness. Due to the potential for side effects such as drowsiness and dizziness, official warnings state that individuals should avoid driving or operating machinery until they know how the medication affects their alertness and coordination.


Q: How is the need for First Progesterone generally determined by a healthcare provider?

The need for this medication is typically determined by a healthcare provider based on a thorough review of clinical history and symptoms. Diagnostic tools, such as a progesterone blood test, are often used to evaluate hormone levels, confirm that ovulation has occurred, or determine the cause of abnormal uterine bleeding.


Q: Does the use of First Progesterone have any known effect on a person's libido (sex drive)?

Some hormonal research suggests that a patient's libido (sex drive) may be affected by changes in progesterone levels. This can manifest as a lowered sex drive, which is considered a potential, expected hormonal effect that may be observed during the course of treatment.


Q: Does First Progesterone protect against osteoporosis?

Progesterone is a component used in Hormone Replacement Therapy (HRT) regimens that are studied for their role in addressing bone loss. Research indicates these treatments may contribute to the maintenance of bone mineral density, particularly when used in combination with estrogen.

How should First Progesterone be stored and disposed of?

Official Storage and Disposal Requirements

Storage Conditions

Progesterone must be stored at controlled room temperature, typically between 15 C and 30 C (59 F and 86 F). It is essential to keep the medicine dry and store it in its original, tightly closed container to maintain its stability. Some formulations should not be refrigerated or frozen. For safety, the product is required to be stored locked up and out of the reach of children.


Disposal Instructions

Disposal must be conducted strictly in accordance with local, national, and international regulations. The product is classified as very toxic to aquatic life with long-lasting effects. Therefore, it is mandatory to avoid release to the environment, including preventing the medicine from entering drains or sewage systems. Unused or expired medication should be taken to a designated collection point.

Attention! Always consult to a doctor or pharmacist before using pills or medicines.

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