Introduction
Norethindrone and mestranol, components of early oral contraceptives, have a significant history in the pharmaceutical market. This article delves into the market dynamics and financial trajectory of these drugs, from their introduction to their current status.
Historical Context
Discovery and Introduction
Mestranol, discovered in 1956, was the estrogen component in the first oral contraceptive, Enovid, developed by G. D. Searle & Company. It was introduced in 1957, marking a revolutionary change in birth control methods[2].
Market Impact
Initial Success
The introduction of Enovid, which combined norethynodrel (a progestogen) and mestranol, was highly successful. It was 100% effective as a contraceptive and medically accepted by 91% of patients in early clinical trials[1].
Expansion and Competition
As the first oral contraceptive, Enovid dominated the market initially. However, with the development of other oral contraceptives, the market expanded, and competition increased. Other brands like Ortho-Novum and Norinyl, also containing norethindrone and mestranol, entered the market[2][4].
Regulatory and Safety Concerns
Venous Thromboembolism
In the late 1960s, concerns about the increased risk of venous thromboembolism associated with estrogen-containing oral contraceptives led to a significant shift in the market. Mestranol was largely replaced by ethinylestradiol, which was considered to be more potent and potentially safer at lower doses[2].
Financial Trajectory
Initial Revenue and Growth
The introduction of Enovid generated substantial revenue for G. D. Searle & Company. The drug's effectiveness and the growing demand for oral contraceptives drove sales, making it a lucrative market segment.
Decline and Replacement
As ethinylestradiol became the preferred estrogen component, the sales of mestranol-containing contraceptives declined. By 1969, most combined oral contraceptives had switched to ethinylestradiol, significantly reducing the market share of norethindrone and mestranol combinations[2].
Current Market Status
Limited Availability
Today, mestranol remains available only in a few countries, including the United States, the United Kingdom, Japan, and Chile. It is marketed in combination with progestins like norethisterone but is no longer a dominant player in the oral contraceptive market[2].
Side Effects and Medical Acceptance
Common Side Effects
Despite its effectiveness, norethindrone and mestranol combinations have been associated with side effects such as breakthrough bleeding, nausea, and weight gain. These side effects, although diminishing with continued use, have impacted patient compliance and market acceptance[4].
Research and Development
Male Contraceptive Studies
Mestranol has been studied as a potential male contraceptive, showing high effectiveness in suppressing gonadotropin levels and reducing sperm count. However, the associated side effects, such as gynecomastia and decreased libido, made it unacceptable for male use[2].
Environmental Impact
Presence in Wastewater
Recent studies have identified mestranol in wastewater treatment plants, contributing to estrogenic activity in the environment. This has raised concerns about the long-term ecological impact of these drugs[2].
Market Trends and Future Outlook
Shift to New Formulations
The market has shifted towards newer formulations with different estrogen and progestogen components, which are considered safer and more effective. This trend is expected to continue, further reducing the market share of norethindrone and mestranol combinations.
Niche Market
While norethindrone and mestranol are no longer mainstream, they still serve a niche market in countries where they are available. This niche market, although small, ensures some level of financial sustainability for these drugs.
Key Takeaways
- Historical Significance: Norethindrone and mestranol were pivotal in the development of oral contraceptives.
- Market Impact: Initial success was followed by a decline due to safety concerns and the introduction of ethinylestradiol.
- Current Status: Limited availability in a few countries, with a niche market presence.
- Side Effects: Associated with breakthrough bleeding, nausea, and weight gain.
- Research: Studied as a male contraceptive but found unacceptable due to side effects.
FAQs
What was the first oral contraceptive containing norethindrone and mestranol?
The first oral contraceptive containing norethindrone and mestranol was Enovid, introduced in 1957.
Why was mestranol largely replaced by ethinylestradiol?
Mestranol was largely replaced by ethinylestradiol due to concerns about the increased risk of venous thromboembolism associated with estrogen-containing oral contraceptives.
What are the common side effects of norethindrone and mestranol combinations?
Common side effects include breakthrough bleeding, nausea, and weight gain.
Is mestranol still used today?
Yes, mestranol is still used today, although it is available only in a few countries and is no longer a dominant player in the oral contraceptive market.
What environmental concerns are associated with mestranol?
Mestranol has been identified in wastewater treatment plants, contributing to estrogenic activity in the environment.
Sources
- Flowers CE. Effects of New Low-Dosage Form of Norethynodrel-Mestranol: Clinical Evaluation and Endometrial Biopsy Study. JAMA. 1964;188(13):1115–1120. doi:10.1001/jama.1964.03060390017005
- Mestranol - Wikipedia
- Oral contraceptives, norethindrone and mestranol: effects on tissue ... PubMed
- An Oral Contraceptive: Norethindrone With Mestranol (Ortho-Novum). JAMA. 1964;187(9):664–665. doi:10.1001/jama.1964.03060220038012
- Mestranol - an overview | ScienceDirect Topics
