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Clinical Tests of Estrogen Injections on Women with Abnormal Menstrual Cycles During the Early 1920s by Jean Paul Pratt and Edgar Allen
In the early twentieth century US, Jean Paul Pratt and Edgar Allen conducted clinical experiments on women who had abnormal menstrual cycles. During the clinical tests, researchers injected the hormone estrogen into their patients to alleviate their menstrual ailments, which ranged from irregular cycles to natural menopause. The hormone estrogen plays a prominent role in the menstrual cycle by signaling the tissue lining the uterus (endometrium) to thicken in preparation for possible pregnancy.
The figure depicts three different molecular structures of estrogen found in mammals’ that differ by the arrangement of bonds and side groups. The molecular structures of the three estrogen molecules differ by the arrangement of chemical bonds and side groups attached to the core steroid structure, cholesterol, which contains three cyclohexane rings and one cyclopentane ring.
Subject: Theories, Processes, Reproduction
Eugen Steinach (1861–1944)
Eugen Steinach researched sex hormones and their effects on mammals in the late nineteenth and early twentieth centuries in Europe. He experimented on rats by removing their testicles and implanting them elsewhere in their bodies, and he found that the testes interstitial cells produce male sex hormones. He developed the Steinach Rejuvenation Procedure, which he claimed could rejuvenate men by increasing their production of sex hormones. Steinach’s work on female sex hormones and on ovarian extracts led to the development of the first standardized injectable estrogen.
The Effects of Diethylstilbestrol on Embryonic Development
Estrogen plays a key role in the regulation of gene transcription. This is accomplished by its ability to act as a ligand and to bind to specific estrogen receptor (ER) molecules, such as ERα and ERβ, which act as nuclear transcription factors. There are three major nuclear estrogen receptor protein domains: the estrogen binding domain, the protein interaction domain, and the DNA binding domain.
Estrogen and the Menstrual Cycle in Humans
Estrogen is the primary sex hormone in women and it functions during the reproductive menstrual cycle. Women have three major types of estrogen: estrone, estradiol, and estriol, which bind to and activate receptors within the body. Researchers discovered the three types of estrogen over a period of seven years, contributing to more detailed descriptions of the menstrual cycle. Each type of estrogen molecule contains a slightly different arrangement or number of atoms that in turn causes some of the estrogens to be more active than others.
Subject: Theories, Reproduction
"Risks and Benefits of Estrogen Plus Progestin in Healthy, Postmenopausal Women: Principal Results from the Women's Health Initiative Randomized Controlled Trial" (2002), by Jacques Rossouw et al.
In 2002, the Writing Group for the Women's Health Initiative Investigators published the article Risks and Benefits of Estrogen Plus Progestin in Healthy, Postmenopausal Women: Principal Results from the Women's Health Initiative Randomized Controlled Trial in The Journal of the American Medical Association.
Action of MER-25 and of Clomiphene on the Human Ovary (1963)
Between 1958 and 1962, physicians Olive W. Smith, George V. Smith, and Robert W. Kistner performed experiments that demonstrated the effects of the drugs MER-25 and clomiphene citrate on the female human body. MER-25 and clomiphene citrate are drugs that affect estrogen production in women. At the time of the experiment, researchers did not know which organ or organs the drugs affected, the ovaries and/or the anterior pituitary gland.
Edgar Allen and Edward A. Doisy's Extraction of Estrogen from Ovarian Follicles, (1923)
In the early 1920s, researchers Edgar Allen and Edward Adelbert Doisy conducted an experiment that demonstrated that ovarian follicles, which produce eggs in mammals, also contain and produce what they called the primary ovarian hormone, later renamed estrogen. In their experiment, Doisy and Allen extracted estrogen from the ovarian follicles of hogs and proved that they had isolated estrogen by using a measurement later renamed the Allen-Doisy test.
Edgar Allen (1892–1943)
Edgar Allen identified and outlined the role of female sex hormones and discovered estrogen in the early 1900s in the US. In 1923, Allen, through his research with mice, isolated the primary ovarian hormone, later renamed estrogen, from ovarian follicles and tested its effect through injections in the uterine tissues of mice. Allen’s work on estrogen, enabled researchers to further study hormones and the endocrine system.
Leuprorelin as a Treatment for Endometriosis
Leuprolide acetate, or leuprorelin, is a manufactured drug that has been prescribed as a treatment for endometriosis, a medical condition in which body tissue that typically lines the uterus grows outside of the uterus, since 1989. Leuprorelin is a modified version of a gonadotropin-releasing hormone, a type of hormone that helps regulate the female menstrual cycle. The drug inhibits the production of estrogen, a female sex hormone that enables endometrial gland growth.
"Adenocarcinoma of the Vagina: Association of Maternal Stilbestrol Therapy with Tumor Appearance in Young Women" (1971), by Arthur L. Herbst, et al.
Published in 1971, Adenocarcinoma of the Vagina: Association of Maternal Stilbestrol Therapy with Tumor Appearance in Young Women, by Arthurs L. Herbst and colleagues, was the first piece of literature connecting maternal use of the drug diethylstilbestrol (DES), also called stilbestrol, with the development of a rare and severe form of vaginal cancer in young women. Diethylstilbestrol was later classified as an endocrine disruptor, a substance that disrupts the hormonal function of the body in those exposed to it during development or later in life.
Edward Charles Dodds (1899-1973)
Edward Charles Dodds researched the function and effects of natural and artificial hormones on the endocrine system in England during the twentieth century. Though he first worked with hormones such as insulin, Dodds focused on the effects of estrogen in the body and how to replicate those effects with artificial substances. In 1938, along with chemist Robert Robinson, Dodds synthesized the first synthetic estrogen called diethylstilbestrol.
The Effects of Bisphenol A on Embryonic Development
Bisphenol A (BPA) is an organic compound that was first synthesized by Aleksandr Dianin, a Russian chemist from St. Petersburg, in 1891. The chemical nomenclature of BPA is 2,2-bis (4-hydroxyphenyl) propane. The significance of this synthesized compound did not receive much attention until 1936, when two biochemists interested in endocrinology, Edward Dodds and William Lawson, discovered its ability to act as an estrogen agonist in ovariectomized, estrogen-deficient rats.
Subject: Disorders, Reproduction
Amenorrhea as a Menstrual Disorder
Amenorrhea is considered a type of abnormal menstrual bleeding characterized by the unexpected absence of menstrual bleeding, lasting three months or longer. Menstrual bleeding typically happens approximately once a month when blood and endometrial tissue, or tissue lining the inside of the uterus, sheds from the uterus through the vagina. Menstruation is expected to stop with pregnancy, breastfeeding, and menopause, or the natural cessation of the menstrual cycle at an older age.
Subject: Disorders, Reproduction
Katharina Dorothea Dalton (1916–2004)
Katharina Dorothea Dalton was a physician in England in the twentieth century who defined premenstrual syndrome (PMS) as a cluster of symptoms suspected to begin one to two weeks before menstruation and disappear upon the onset of a new menstrual cycle. Prior to Dalton, there was little research on pre-menstrual issues and those that existed linked the problem to excessive water retention or estrogen. Dalton hypothesized that PMS resulted from a deficiency in the hormone progesterone and advocated for hormone replacement therapy to lessen the symptoms of the syndrome.
"The Premenstrual Syndrome" (1953), by Raymond Greene and Katharina Dalton
In 1953, Raymond Greene and Katharina Dalton, who were doctors in the UK, published The Premenstrual Syndrome in the British Medical Journal. In their article, Dalton and Greene established the term premenstrual syndrome (PMS). The authors defined PMS as a cluster of symptoms that include bloating, breast pain, migraine-headache, fatigue, anxiety, depression, and irritability. The article states that the symptoms begin one to two weeks before menstruation during the luteal phase of the menstrual cycle, and they disappear upon the onset of the menstrual period.
Subject: Publications, Reproduction
"Experimental Studies on Congenital Malformations" (1959), by James G. Wilson
The article Experimental Studies on Congenital Malformations was published in the Journal of Chronic Diseases in 1959. The author, James G. Wilson, studied embryos and birth defects at the University of Florida Medical School in Gainesville, Florida. In his article, Wilson reviewed experiments on birds and mammals from the previous forty years to provide general principles and guidelines in the study of birth defects and teratogens, which are things that cause birth defects.
Barbara Seaman (1935–2008)
Barbara Seaman was a writer, investigator, and advocate for female healthcare rights during the twentieth century in the United States. Seaman’s work addressed the gendered prejudice she observed in the US healthcare system and argued that women of the 1960s lacked the proper tools to make informed decisions about pregnancy care, breastfeeding, childbirth, and contraception. Seaman wrote the book The Doctor’s Case Against the Pill in 1969 to expose the dangers in prescribing and consuming high doses of estrogen in the form of birth control.
US Endocrine Disruptor Screening Program
In 1996, the US Congress mandated that the US Environmental Protection Agency (EPA) create and regulate the Endocrine Disruptor Screening Program. The program tests industrial and agricultural chemicals for hormonal impacts in humans and in wildlife that may disrupt organisms' endocrine systems. The endocrine system regulates the release of small amounts of chemical substances called hormones to keep the body functioning normally.
“Cardiovascular Risk Associated With the Use of an Etonogestrel-Containing Vaginal Ring” (2013), by Jürgen Dinger, Sabine Möhner, and Klaas Heinemann
In October 2013, Jürgen Dinger, Sabine Möhner, and Klaas Heinemann published the article “Cardiovascular Risk Associated With the Use of an Etonogestrel-Containing Vaginal Ring,” hereafter “Cardiovascular Risk,” in the journal Obstetrics and Gynecology. The authors enrolled patients in the study who were new users of either a vaginal contraceptive ring known as NuvaRing or a combined oral contraceptive pill. A combined oral contraceptive pill contains a formulation of the hormones progesterone and estrogen.
Subject: Technologies, Reproduction
Diethylstilbestrol (DES) in the US
Diethylstilbestrol (DES) is an artificially created hormone first synthesized in the late 1930s. Doctors widely prescribed DES first to pregnant women to prevent miscarriages, and later as an emergency contraceptive pill and to treat breast cancer. However, in 1971, physicians showed a link between DES and vaginal cancer during puberty in the children of women who had taken DES while pregnant. Consequently, the US Food and Drug Administration (FDA) banned its use during pregnancy.
Subject: Reproduction, Technologies
The NuvaRing is a self-administered hormonal contraceptive device in the form of a flexible plastic ring that is inserted into the vagina. It releases the hormones etonogestrel and ethinylestradiol, which are synthetic forms of the female reproductive hormones progesterone and estrogen, respectively. The pharmaceutical company Organon first made NuvaRing in the Netherlands in 1980s. The Netherlands first approved it for use in February of 2001, and the United States did the same in October of that year.
Subject: Technologies, Reproduction, Legal
Sindell v. Abbott Laboratories (1980)
Sindell v. Abbott Laboratories was a 1980 California case that established the doctrine of market share liability for personal injury cases. For such liability, when a drug causes personal injury and the manufacturer of the drug cannot be identified, each producer is responsible for paying the settlement in proportion to the percentage of the market they supplied. Judith Sindell and Maureen Rogers brought the case against the producers of diethylstilbestrol (DES), which their mothers had taken during pregnancy to prevent miscarriage and other complications.
Clomiphene citrate, more commonly known by its brand names Clomid and Serophene, is a medication prescribed to women to stimulate ovulation in order to treat infertility. It stimulates ovulation in women who do not ovulate or ovulate irregularly. This drug was created by Dr. Frank Palopoli in 1956 while he worked for Merrell Company. It first successfully induced ovulation in women in 1961 and was approved by the Federal and Drug Administration (FDA) in 1967.
"Developmental Effects of Endocrine-Disrupting Chemicals in Wildlife and Humans" (1993), by Theo Colborn, Frederick S. vom Saal, and Ana M. Soto
Developmental Effects of Endocrine-Disrupting Chemicals in Wildlife and Humans, was published in 1993 in Environmental Health Perspectives. In the article, the authors present an account of two decades' worth of scientific research that describes the effects of certain pollutants on the health of wildlife, domestic animals, and humans, particularly when exposure takes place during embryonic growth. The term endocrine disruptor was coined in the article to describe the chemical pollutants that target the development and function of the endocrine system.