The Effects of Hormonal Contraception on the Voice: History of Its Evolution in the Literature.

OBJECTIVES: Women of reproductive age commonly use hormonal contraceptives, the vocal effects of which have been studied. Otolaryngologists should be aware of this relationship to make recommendations on hormonal contraception as it relates to each patient's voice requirements. METHODS/DESIGN: A comprehensive literature review of PubMed was completed. The terms "contraception," "vocal folds," "vocal cords," and "voice" were searched in various combinations. Articles from 1971 to 2015 that addressed the effects of contraception on the vocal folds were included. RESULTS: In total, 24 articles were available for review. Historically, contraception was believed to affect the voice negatively. However, more recent studies using low-dose oral contraceptive pills (OCPs) show that they stabilize the voice. However, stabilization generally occurs only during sustained vowel production; connected speech appears unaffected. Therefore, singers may be the only population that experiences clinically increased vocal stability as a result of taking hormonal contraceptives. Only combined OCPs have been studied; other forms of hormonal contraception have not been evaluated for effects on the voice. Significant variability exists between studies in the physical attributes of patients and parameters tested. CONCLUSIONS: Hormonal contraception likely has no clinically perceptible effects on the speaking voice. Singers may experience increased vocal stability with low-dose, combined OCP use. Other available forms of contraception have not been studied. Greater consistency in methodology is needed in future research, and other forms of hormonal contraception require study.

History of oral contraceptive drugs and their use worldwide.

The first hormonal pill, called Enovid(®), was approved by the Federal Drug Administration (FDA) in May 1960. It contained mestranol and norethisterone. Over the years, oral contraceptives have evolved through gradual lowering of ethinyl estradiol (EE) content, introduction of 17ß estradiol, and many different progestins. The standard regimen allows for 21 days of pill containing steroids and a pill-free interval of 7 days. Recently, continuous or extended regimens have been approved. In order to improve compliance, alternative routes of combined oral contraceptive (COC) administration have been developed such as vaginal or transdermal routes. In 2009, according to the United Nations, the mean global percentage using contraception in women who are married or in union was 62.7%. COC represented 8.8% of contraceptive prevalence, reaching 15.4% in more developed countries. More than 100 million women worldwide use COCs. However, each year, many unintended pregnancies occur, indicating that contraception still needs to be promoted.

An overview of the development of combined oral contraceptives containing estradiol: focus on estradiol valerate/dienogest.

Natural estrogens such as estradiol (E(2)) or its valerate ester (E(2)V) offer an alternative to ethinyl estradiol (EE). E(2)-containing combined oral contraceptives (COCs) have demonstrated sufficient ovulation inhibition and acceptable contraceptive efficacy. However, earlier formulations were generally associated with unacceptable bleeding profiles. Two E(2)V-containing preparations have been approved to date for contraceptive use: E(2)V/cyproterone acetate (CPA) (Femilar(®); only approved in Finland and only in women >40 years or women aged 35-40 years in whom a COC containing EE is not appropriate) and E(2)V/dienogest (DNG; Qlaira(®)/Natazia(®)). The objective of the current review is to provide an overview of the development of COCs containing natural estrogen, highlighting past issues and challenges faced by earlier formulations, as well as the current status and future directions. The majority of information to date pertains to the development of E(2)V/DNG.

The evolution of combined oral contraception: improving the risk-to-benefit ratio.

Since its introduction in 1960, the combined oral contraceptive (COC) pill has become one of the most widely and frequently used methods of contraception worldwide. Although highly effective, early COC formulations were associated with significant adverse effects and unacceptable cardiovascular risk. Improvements in tolerability and safety have been achieved, without compromises in effectiveness, primarily via hormone dosage reductions and the development of several new progestins. Multiphasic COCs and extended-/continuous-cycle COCs have also been introduced, although the clinical advantages of these formulations vs. traditional COCs have yet to be established. Inclusion of natural estrogens such as estradiol valerate and 17ß-estradiol with selective progestins in new combinations that maintain good cycle control is the most recent evolutionary step designed to improve COC tolerability and safety. Vigorous research needs to continue to help guarantee that the unmet need for safe and effective contraception is satisfied in future generations.

50 years of "The Pill": celebrating a golden anniversary.

The past 50 years have seen great advances in combined oral contraceptives (COCs) that have resulted in reduced risks of adverse events and improved cycle control. The most important changes in COCs over time include repeated lowering of the estrogen dose, development of new progestogens, and the reduction or elimination of the pill-free interval. Most recently, formulations that deliver estradiol in lieu of ethinylestradiol have been introduced. The advantages of COCs generally far outweigh the disadvantages. Current options in oral contraception include a wide spectrum of products that enable clinicians to choose the most appropriate formulation for individual women. This article summarises the advances in oral contraceptives over time and describes the most current clinical data regarding the use of COCs.

Forty years of combined oral contraception: the evolution of a revolution.

The combined oral contraceptive (COC) pill has become an integral part of fertility choice in almost every country since its introduction in 1960 in the United States. It was the first contraceptive method to provide sexual freedom of choice for women through reliable personal, private control of fertility. Modern, very low-dose pills have maintained a high degree of contraceptive efficacy, but the margin for error in pill-taking appears much smaller. These COCs have a much lower incidence of side effects and serious complications than early high-dose COCs. Serious health risks from venous thromboembolism are rare, and not measurably higher for pills containing third-generation compared with earlier progestogens. Most women feel very well taking modern COCs, but myths about these drugs still abound. Most non-contraceptive health benefits of COCs are still not widely appreciated in spite of much evidence. Controversy still persists over the association between COC use and breast cancer. Although slightly more breast cancers are detected in current COC users (relative risk 1.24; 95% CI, 1.15-1.33), they are less advanced and less aggressive. Some women have pre-existing medical risk factors for COC use, and a detailed history for cardiovascular risk factors is one of the most important precautions.

Oral contraceptives in the United States: trends in content and potency.

Data from the National Prescription Audit, a nationwide pharmaceutical marketing research data base, were reviewed to study changes in the type of oral contraceptives marketed in the US, their content and their relative oestrogen and progestin potency over the 21-year time period of 1964-84. Three major types and 42 brands of oral contraceptives were marketed in the US during this time period. All oral contraceptives dispensed in the US have contained one of nine different progestins and one of two oestrogens or, in the case of the progestin-only pills, no oestrogen at all. A comprehensive classification listing all 42 brands of oral contraceptives by content and strength is presented. Secular changes in oral contraceptive potency are described in terms of a categorization scheme which simultaneously ranks both the oestrogen and progestin potencies of each oral contraceptive. Over the time period studied, oral contraceptives have evolved from high strength, high potency drugs to much lower strength, lower potency drugs. The epidemiological implications of these shifts in oral contraceptive content and potency are discussed.