Estradiol

Estradiol Market Outlook

The global Estradiol market is projected to reach approximately USD 8.5 billion by 2035, with a compound annual growth rate (CAGR) of around 4.5% during the forecast period of 2025 to 2035. This growth can be attributed to the increasing prevalence of hormone-related disorders and the rising demand for hormone replacement therapies across diverse demographics. Additionally, the growing acceptance and awareness of women's health issues, coupled with advancements in biotechnology and pharmaceutical innovations, are driving the market. Furthermore, the surge in the aging population and the rising incidence of conditions such as osteoporosis and menopausal symptoms are expected to contribute significantly to the increasing demand for estradiol-based treatments. These dynamics present a robust framework for market expansion, emphasizing the importance of addressing both current and emerging healthcare needs.

Growth Factor of the Market

Several key growth factors are propelling the Estradiol market forward. Firstly, the increasing global awareness surrounding women’s health issues, particularly those related to menopause and hormone imbalances, has led to a greater demand for effective treatment options. Furthermore, advancements in delivery systems, such as transdermal patches and gels, have enhanced patient compliance and satisfaction, driving market growth. Secondly, the rise in lifestyle-related diseases that affect hormonal balance has necessitated the need for estradiol therapies. Thirdly, the growing acceptance of hormone replacement therapy (HRT) as a viable option for improving the quality of life in menopausal women is also a significant growth driver. Moreover, government initiatives focused on women's health and increasing healthcare expenditures further support market growth. Finally, the ongoing research and development efforts aimed at creating novel formulations and drug delivery mechanisms are expected to sustain the momentum of the Estradiol market for years to come.

Key Highlights of the Market

• The global Estradiol market is expected to grow significantly, reaching USD 8.5 billion by 2035.
• The market is being driven by increasing awareness of women's health issues and hormone-related disorders.
• Advancements in drug delivery systems, such as patches and gels, are enhancing patient adherence.
• Government initiatives and rising healthcare spending are fostering a supportive environment for growth.
• Continuous research and innovation in estradiol formulations are likely to open new avenues for market expansion.

By Product Type

Oral Tablets:

Oral tablets are one of the most commonly used forms of estradiol delivery, making them a significant segment in the Estradiol market. They offer a convenient option for patients to manage their hormonal therapy, providing accurate dosing and ease of use. The ability to easily adjust dosages and the widespread familiarity with oral medications contribute to their popularity. Additionally, ongoing advancements in the formulation of oral tablets have improved their effectiveness, leading to increased patient satisfaction. This segment is expected to witness steady growth as more healthcare providers recommend oral tablets for conditions such as menopause and hormone replacement therapies, solidifying their role in the overall market.

Transdermal Patches:

Transdermal patches represent a growing segment within the Estradiol market, providing an innovative and user-friendly method of hormone delivery. These patches allow for the continuous release of estradiol through the skin, which can help maintain stable hormone levels and minimize side effects associated with oral administration. The convenience of not having to remember daily doses makes transdermal patches an attractive option for many patients. Moreover, the technological advancements in transdermal systems have enhanced their absorption rates and effectiveness. As patients increasingly seek alternatives that offer improved compliance and convenience, transdermal patches are expected to gain a larger market share in the coming years.

Injections:

Injections are another important method of administering estradiol, particularly for patients requiring immediate therapeutic effects or those who cannot tolerate oral medications. This segment caters to a niche market but is significant for specific applications, such as gender affirmation therapy and severe hormone deficiencies. Injectable formulations can offer rapid hormonal adjustments and are often used in clinical settings where precise control over hormone levels is necessary. Although this route of administration may come with limitations in terms of patient preference and convenience, it remains essential for targeted therapies, and demand is likely to persist, supported by the ongoing focus on personalized medicine.

Gels:

The gel segment is becoming increasingly popular due to its flexible application and user-friendly nature. Estradiol gels provide a non-invasive method of hormone delivery that allows patients to apply a controlled dose of estradiol directly to the skin. This method eliminates the need for needles and can result in more consistent absorption compared to some oral medications. The growth of this segment can also be attributed to the rising trend of self-administration, where patients prefer at-home therapies. As more studies highlight the efficacy and ease of use of estradiol gels, this segment is anticipated to expand significantly in the Estradiol market.

Implants:

Implants are a less common but effective method of delivering estradiol, suitable for long-term hormone therapy. These devices are placed subcutaneously and provide continuous hormone release over an extended period, which can last several months. The primary advantage of this delivery method is that it minimizes the need for frequent dosing, enhancing patient adherence to therapy. Moreover, implants can be tailored to individual hormonal needs, providing a more personalized treatment experience. Although the market for implants is currently smaller compared to other delivery methods, it has the potential for growth as healthcare providers increasingly recognize the benefits of long-acting therapies in managing hormonal imbalances.

By Application

Hormone Replacement Therapy:

Hormone Replacement Therapy (HRT) is one of the largest applications for estradiol, primarily targeting menopausal women experiencing symptoms such as hot flashes, night sweats, and mood changes. HRT aims to restore hormonal balance, alleviating discomfort and improving the overall quality of life. The growing acceptance and understanding of HRT among both healthcare professionals and patients have led to increased demand for estradiol therapies. Additionally, educational campaigns about the benefits and risks associated with HRT have contributed to more informed decision-making regarding treatment options. As the population ages and more women seek effective management of menopausal symptoms, the HRT application of estradiol is expected to continue its upward trajectory.

Contraception:

The use of estradiol in contraceptive methods is another significant application driving market growth. Estradiol is commonly combined with progestins in various hormonal contraceptives, including pills, patches, and rings. These contraceptive methods provide effective pregnancy prevention while also offering additional health benefits, such as regulating menstrual cycles and reducing the risk of certain reproductive health issues. The increasing demand for effective contraceptive options, combined with growing awareness of reproductive health, has spurred growth in this segment. Furthermore, as societal attitudes toward family planning evolve and more women prioritize reproductive autonomy, the contraceptive application of estradiol is expected to expand significantly.

Osteoporosis Treatment:

Estradiol plays a crucial role in the treatment of osteoporosis, particularly among post-menopausal women who are at a higher risk of developing this condition. By restoring estrogen levels, estradiol helps maintain bone density and reduce the likelihood of fractures. The increasing prevalence of osteoporosis, coupled with the aging population, has intensified the demand for effective treatment options, with estradiol being a key component. Healthcare providers are increasingly recognizing the importance of addressing bone health as part of comprehensive women's health care, further solidifying the role of estradiol in osteoporosis treatment. As awareness of osteoporosis rises, the application of estradiol in managing this condition is set to grow.

Gender Affirmation:

Gender affirmation therapy is an important application for estradiol, supporting individuals undergoing transitions in gender identity. Estradiol is crucial in developing secondary sexual characteristics for transgender women, making it a key component of gender-affirming hormone therapy. The increasing visibility and acceptance of transgender individuals have led to a rising demand for gender affirmation treatments, including estradiol. As healthcare providers become more knowledgeable about transgender health and the specific needs of this population, the market for estradiol in gender affirmation is expected to grow. Additionally, ongoing advocacy for transgender rights and access to healthcare further enhances the potential market for estradiol in this application.

By Distribution Channel

Hospitals:

The hospital distribution channel for estradiol products remains a significant segment, as hospitals often provide comprehensive care for patients with complex health needs. Patients typically receive estradiol therapies as part of a broader treatment plan, especially in cases requiring immediate medical attention or specialized care, such as hormone therapies related to surgery or specific medical conditions. The advantage of hospital distribution lies in the professional oversight and monitoring that patients receive, ensuring that therapies are administered safely and effectively. The trend toward patient-centered care in hospitals is expected to bolster the demand for estradiol products as part of integrated healthcare solutions.

Retail Pharmacies:

Retail pharmacies play a vital role in the distribution of estradiol products, particularly oral tablets and topical treatments. These pharmacies provide easy access for patients seeking prescriptions and over-the-counter options for estradiol therapies. The convenience of obtaining medications from local pharmacies, along with the ability to seek consultations from pharmacists, enhances patient engagement and adherence to treatment plans. As patient preferences shift towards more accessible healthcare solutions, the retail pharmacy segment is likely to experience continuous growth, especially with the increasing demand for women's health products.

Online Pharmacies:

The rise of online pharmacies is transforming the way estradiol products are distributed, offering patients a convenient alternative to traditional pharmacy channels. Online platforms provide the ability to order medications from the comfort of home, often with greater privacy and discretion. This is particularly appealing for individuals seeking hormone therapies, as they may prefer a more confidential approach to managing their health. By leveraging technology, online pharmacies can also ensure prompt delivery and often offer competitive pricing. As e-commerce continues to reshape the healthcare landscape, the online pharmacy segment for estradiol products is anticipated to grow significantly, catering to the needs of tech-savvy consumers.

Drug Stores:

Drug stores remain a crucial distribution channel for estradiol products, serving as one-stop shops for a variety of health and wellness needs. These establishments typically carry a wide range of over-the-counter and prescription medications, including estradiol therapies, making them accessible to a broad customer base. The convenience of drug stores, with their extended hours and varied product offerings, appeals to consumers looking for quick and straightforward solutions for their health concerns. As more people become proactive about their health, the drug store channel is expected to maintain its importance in the distribution of estradiol products, ensuring that patients have easy access to necessary therapies.

By Ingredient Type

Estradiol Valerate:

Estradiol valerate is a commonly used form of estradiol in hormone therapies, recognized for its efficacy and favorable pharmacokinetic properties. Often administered via intramuscular injections or as part of oral contraceptives, estradiol valerate has gained popularity due to its ability to provide stable hormone levels and effective symptom relief. Its versatility in various formulations enhances its market potential, particularly in hormone replacement therapy and contraception. As awareness of the benefits of estradiol valerate grows, its utilization in both clinical and outpatient settings is expected to increase, supporting the overall growth of the estradiol market.

Estradiol Cypionate:

Estradiol cypionate is another prevalent form used primarily in injectable hormone therapies. This ingredient is known for providing a longer duration of action compared to other estradiol formulations, making it ideal for patients requiring sustained hormonal support. Its application in gender affirmation therapy and hormone replacement therapy has bolstered its demand, as practitioners often favor its predictable pharmacodynamics. The growing acceptance of injectable therapies, coupled with ongoing research highlighting the benefits of estradiol cypionate, is likely to enhance its market share within the estradiol segment.

Estradiol Hemihydrate:

Estradiol hemihydrate is primarily utilized in oral formulations and is recognized for its efficacy in managing menopausal symptoms and hormonal imbalances. This ingredient is often preferred for its effectiveness in improving quality of life for post-menopausal women. As patient preferences increasingly lean towards oral therapies for convenience and compliance, the market for estradiol hemihydrate is expected to grow. Additionally, ongoing clinical studies that explore the benefits and applications of estradiol hemihydrate in various therapeutic settings will likely further drive its utilization in hormone therapies.

Estradiol Acetate:

Estradiol acetate is notable for its role in hormone replacement therapy and is often used in combination with other hormones to enhance therapeutic efficacy. This ingredient is valued for its compatibility with various administration routes, including oral and transdermal applications. The demand for estradiol acetate is expected to rise, particularly in markets where personalized hormone therapies are gaining prominence, as it can be tailored to meet individual patient needs. With the continuous exploration of innovative formulations and delivery systems, estradiol acetate's market presence is anticipated to grow steadily.

Estradiol Benzoate:

Estradiol benzoate is primarily used in injectable formulations and is known for its rapid onset of action, making it an effective choice for those requiring immediate therapeutic effects. Its use in both hormone replacement therapy and gender affirmation treatments underscores its versatility. As healthcare providers increasingly recognize the importance of individualized treatment approaches, the demand for estradiol benzoate is likely to rise. Furthermore, the expansion of clinical guidelines supporting its use in various applications will contribute to its overall growth in the estradiol market.

By Region

The Estradiol market exhibits significant regional variances, with North America leading the market share due to the high prevalence of hormone-related disorders and an established healthcare infrastructure. In 2023, North America accounted for approximately 40% of the global market, driven by the increasing demand for hormone replacement therapies and a growing aging population. The region's focus on women's health and well-being further bolsters the prospects for estradiol products. Additionally, the presence of numerous pharmaceutical companies and ongoing research initiatives in the United States and Canada are expected to support consistent market growth, with a projected CAGR of 4.7% through 2035.

Europe holds the second-largest market share, contributing around 30% to the global Estradiol market, primarily attributed to the increasing awareness of women's health issues and a favorable regulatory environment for hormone therapies. Countries such as Germany, France, and the UK are at the forefront of this growth, with healthcare systems that support innovative treatment options. Additionally, the rising number of menopausal women in Europe is further fueling the demand for estradiol therapies. The Asia Pacific region is also emerging as a significant player, with a projected CAGR of 5.0%, driven by improving healthcare access and a growing focus on women's health. As awareness continues to spread, increasing investments in healthcare infrastructure will likely enhance market opportunities in this region.

Opportunities

The Estradiol market is poised for substantial opportunities as healthcare systems around the world prioritize women's health and hormonal therapies. With an increasing population of aging women experiencing menopause, there is a pressing need for effective treatment solutions, which presents companies with the chance to innovate and expand their product lines. Furthermore, the growing acceptance of hormone replacement therapies as a means to improve quality of life and manage symptoms associated with menopause is a critical opportunity that can be leveraged by pharmaceutical companies. By developing new formulations and delivery methods, companies can cater to diverse consumer preferences and enhance patient adherence to therapy.

Moreover, the global focus on mental health and overall well-being has resulted in increased interest in the psychological aspects of hormonal treatments. This presents an opportunity for market players to collaborate with healthcare providers to educate patients on the benefits of estradiol therapies, thereby encouraging adoption. The rise of telemedicine and online healthcare platforms also opens doors for innovative marketing strategies, allowing companies to reach consumers directly and offer personalized treatment plans. Overall, the combination of an aging population, increased awareness of women's health issues, and advancements in healthcare technology positions the Estradiol market for sustained growth and expansion in the coming years.

Threats

Despite the favorable growth trajectory of the Estradiol market, several threats could impact its progress. The most significant challenge comes from the ongoing debates regarding the safety of hormone replacement therapies, fueled by research linking HRT to certain health risks, such as cardiovascular diseases and certain types of cancer. These concerns can discourage patients from pursuing necessary treatments and may lead to increased regulatory scrutiny, potentially stifling market growth. Additionally, the availability of alternative treatment options, including herbal supplements and non-hormonal therapies, poses a competitive threat to the market as patients seek perceived safer alternatives.

Furthermore, fluctuations in regulatory guidelines across different regions can create uncertainty for manufacturers, complicating product development and market entry strategies. Intellectual property issues and patent expirations can also lead to increased competition from generic versions of estradiol products, potentially driving down prices and profit margins. Manufacturers must remain agile and responsive to these market dynamics to retain their competitive edge while ensuring compliance with evolving regulatory frameworks. Addressing these threats proactively will be crucial for sustaining growth in the Estradiol market.

Competitor Outlook

• AbbVie Inc.
• Teva Pharmaceutical Industries Ltd.
• Novartis AG
• Sandoz International GmbH
• Ferring Pharmaceuticals
• Mylan N.V.
• Hikma Pharmaceuticals PLC
• Endo International PLC
• Amgen Inc.
• Bayer AG
• Merck & Co., Inc.
• Pfizer Inc.
• Allergan plc
• Watson Pharmaceuticals, Inc.
• Gedeon Richter Plc.

The competitive landscape of the Estradiol market is characterized by a mix of established pharmaceutical companies and emerging players, all vying for market share in a rapidly evolving healthcare environment. Major companies like AbbVie Inc., Teva Pharmaceutical Industries Ltd., and Novartis AG dominate the landscape, leveraging their extensive research and development capabilities to innovate and expand their product offerings. These companies invest heavily in clinical trials to validate the safety and efficacy of their estradiol formulations, ensuring compliance with stringent regulatory standards. Additionally, strategic partnerships and collaborations within the industry are increasingly common as companies seek to share resources and expertise, allowing for accelerated product development and market entry.

AbbVie Inc., for instance, is known for its robust portfolio of hormone therapies, including estradiol products for both hormone replacement therapy and contraception. The company’s commitment to research and development has positioned it as a leader in the market, driving innovation and meeting the diverse needs of patients. Similarly, Novo Nordisk is recognized for its expertise in hormone therapies and has made significant investments in developing new delivery systems, further enhancing the patient experience with estradiol products.

Novartis AG and Teva Pharmaceutical Industries Ltd. have also made significant strides in the Estradiol market by expanding their product lines and investing in marketing strategies that enhance awareness among end-users. Additionally, these companies are increasingly focusing on patient education and support programs to build trust and improve adherence to therapies. Their proactive approach to addressing the needs of healthcare providers and patients places them in a favorable position to capture a larger share of the market.

• 1 Appendix

  • 1.1 List of Tables
  • 1.2 List of Figures

• 2 Introduction

  • 2.1 Market Definition
  • 2.2 Scope of the Report
  • 2.3 Study Assumptions
  • 2.4 Base Currency & Forecast Periods

• 3 Market Dynamics

  • 3.1 Market Growth Factors
  • 3.2 Economic & Global Events
  • 3.3 Innovation Trends
  • 3.4 Supply Chain Analysis

• 4 Consumer Behavior

  • 4.1 Market Trends
  • 4.2 Pricing Analysis
  • 4.3 Buyer Insights

• 5 Key Player Profiles

  • 5.1 Bayer AG
    • 5.1.1 Business Overview
    • 5.1.2 Products & Services
    • 5.1.3 Financials
    • 5.1.4 Recent Developments
    • 5.1.5 SWOT Analysis
  • 5.2 Amgen Inc.
    • 5.2.1 Business Overview
    • 5.2.2 Products & Services
    • 5.2.3 Financials
    • 5.2.4 Recent Developments
    • 5.2.5 SWOT Analysis
  • 5.3 Mylan N.V.
    • 5.3.1 Business Overview
    • 5.3.2 Products & Services
    • 5.3.3 Financials
    • 5.3.4 Recent Developments
    • 5.3.5 SWOT Analysis
  • 5.4 AbbVie Inc.
    • 5.4.1 Business Overview
    • 5.4.2 Products & Services
    • 5.4.3 Financials
    • 5.4.4 Recent Developments
    • 5.4.5 SWOT Analysis
  • 5.5 Novartis AG
    • 5.5.1 Business Overview
    • 5.5.2 Products & Services
    • 5.5.3 Financials
    • 5.5.4 Recent Developments
    • 5.5.5 SWOT Analysis
  • 5.6 Pfizer Inc.
    • 5.6.1 Business Overview
    • 5.6.2 Products & Services
    • 5.6.3 Financials
    • 5.6.4 Recent Developments
    • 5.6.5 SWOT Analysis
  • 5.7 Allergan plc
    • 5.7.1 Business Overview
    • 5.7.2 Products & Services
    • 5.7.3 Financials
    • 5.7.4 Recent Developments
    • 5.7.5 SWOT Analysis
  • 5.8 Merck & Co., Inc.
    • 5.8.1 Business Overview
    • 5.8.2 Products & Services
    • 5.8.3 Financials
    • 5.8.4 Recent Developments
    • 5.8.5 SWOT Analysis
  • 5.9 Gedeon Richter Plc.
    • 5.9.1 Business Overview
    • 5.9.2 Products & Services
    • 5.9.3 Financials
    • 5.9.4 Recent Developments
    • 5.9.5 SWOT Analysis
  • 5.10 Endo International PLC
    • 5.10.1 Business Overview
    • 5.10.2 Products & Services
    • 5.10.3 Financials
    • 5.10.4 Recent Developments
    • 5.10.5 SWOT Analysis
  • 5.11 Ferring Pharmaceuticals
    • 5.11.1 Business Overview
    • 5.11.2 Products & Services
    • 5.11.3 Financials
    • 5.11.4 Recent Developments
    • 5.11.5 SWOT Analysis
  • 5.12 Hikma Pharmaceuticals PLC
    • 5.12.1 Business Overview
    • 5.12.2 Products & Services
    • 5.12.3 Financials
    • 5.12.4 Recent Developments
    • 5.12.5 SWOT Analysis
  • 5.13 Sandoz International GmbH
    • 5.13.1 Business Overview
    • 5.13.2 Products & Services
    • 5.13.3 Financials
    • 5.13.4 Recent Developments
    • 5.13.5 SWOT Analysis
  • 5.14 Watson Pharmaceuticals, Inc.
    • 5.14.1 Business Overview
    • 5.14.2 Products & Services
    • 5.14.3 Financials
    • 5.14.4 Recent Developments
    • 5.14.5 SWOT Analysis
  • 5.15 Teva Pharmaceutical Industries Ltd.
    • 5.15.1 Business Overview
    • 5.15.2 Products & Services
    • 5.15.3 Financials
    • 5.15.4 Recent Developments
    • 5.15.5 SWOT Analysis

• 6 Market Segmentation

  • 6.1 Estradiol Market, By Application
    • 6.1.1 Hormone Replacement Therapy
    • 6.1.2 Contraception
    • 6.1.3 Osteoporosis Treatment
    • 6.1.4 Gender Affirmation
  • 6.2 Estradiol Market, By Product Type
    • 6.2.1 Oral Tablets
    • 6.2.2 Transdermal Patches
    • 6.2.3 Injections
    • 6.2.4 Gels
    • 6.2.5 Implants
  • 6.3 Estradiol Market, By Ingredient Type
    • 6.3.1 Estradiol Valerate
    • 6.3.2 Estradiol Cypionate
    • 6.3.3 Estradiol Hemihydrate
    • 6.3.4 Estradiol Acetate
    • 6.3.5 Estradiol Benzoate
  • 6.4 Estradiol Market, By Distribution Channel
    • 6.4.1 Hospitals
    • 6.4.2 Retail Pharmacies
    • 6.4.3 Online Pharmacies
    • 6.4.4 Drug Stores

• 7 Competitive Analysis

  • 7.1 Key Player Comparison
  • 7.2 Market Share Analysis
  • 7.3 Investment Trends
  • 7.4 SWOT Analysis

• 8 Research Methodology

  • 8.1 Analysis Design
  • 8.2 Research Phases
  • 8.3 Study Timeline

• 9 Future Market Outlook

  • 9.1 Growth Forecast
  • 9.2 Market Evolution

• 10 Geographical Overview

  • 10.1 Europe - Market Analysis
    • 10.1.1 By Country
      • 10.1.1.1 UK
      • 10.1.1.2 France
      • 10.1.1.3 Germany
      • 10.1.1.4 Spain
      • 10.1.1.5 Italy
  • 10.2 Estradiol Market by Region
  • 10.3 Asia Pacific - Market Analysis
    • 10.3.1 By Country
      • 10.3.1.1 India
      • 10.3.1.2 China
      • 10.3.1.3 Japan
      • 10.3.1.4 South Korea
  • 10.4 Latin America - Market Analysis
    • 10.4.1 By Country
      • 10.4.1.1 Brazil
      • 10.4.1.2 Argentina
      • 10.4.1.3 Mexico
  • 10.5 North America - Market Analysis
    • 10.5.1 By Country
      • 10.5.1.1 USA
      • 10.5.1.2 Canada
  • 10.6 Middle East & Africa - Market Analysis
    • 10.6.1 By Country
      • 10.6.1.1 Middle East
      • 10.6.1.2 Africa

• 11 Global Economic Factors

  • 11.1 Inflation Impact
  • 11.2 Trade Policies

• 12 Technology & Innovation

  • 12.1 Emerging Technologies
  • 12.2 AI & Digital Trends
  • 12.3 Patent Research

• 13 Investment & Market Growth

  • 13.1 Funding Trends
  • 13.2 Future Market Projections

• 14 Market Overview & Key Insights

  • 14.1 Executive Summary
  • 14.2 Key Trends
  • 14.3 Market Challenges
  • 14.4 Regulatory Landscape

Segments Analyzed in the Report

The global Estradiol market is categorized based on

By Product Type

• Oral Tablets
• Transdermal Patches
• Injections
• Gels
• Implants

By Application

• Hormone Replacement Therapy
• Contraception
• Osteoporosis Treatment
• Gender Affirmation

By Distribution Channel

• Hospitals
• Retail Pharmacies
• Online Pharmacies
• Drug Stores

By Ingredient Type

• Estradiol Valerate
• Estradiol Cypionate
• Estradiol Hemihydrate
• Estradiol Acetate
• Estradiol Benzoate

By Region

• North America
• Europe
• Asia Pacific
• Latin America
• Middle East & Africa

Key Players

• AbbVie Inc.
• Teva Pharmaceutical Industries Ltd.
• Novartis AG
• Sandoz International GmbH
• Ferring Pharmaceuticals
• Mylan N.V.
• Hikma Pharmaceuticals PLC
• Endo International PLC
• Amgen Inc.
• Bayer AG
• Merck & Co., Inc.
• Pfizer Inc.
• Allergan plc
• Watson Pharmaceuticals, Inc.
• Gedeon Richter Plc.