In 2008 researchers Daniel Warner and Richard Shine tested the Charnov-Bull model by conducting experiments on the Jacky dragon (Amphibolurus muricatus), in Australia. Their results showed that temperature-dependent sex determination(TSD) evolved in this species as an adaptation to fluctuating environmental temperatures. The Charnov-Bull model, proposed by Eric Charnov and James Bull in 1977, described the evolution of TSD, although the model was, for many years, untested. Many reptiles and some fish exhibit non-genetic sex determination, in which an embryos' environment can influence the sex of the adult organism. Environmental conditions such as humidity or population density can alter sex in some organisms, and a widespread form of non-genetic sex determination is temperature-dependent sex determination. TSD reveals how embryonic development can contribute to the evolution of physiological processes. Researchers have documented TSD in a wide range of species, and they continue to investigate how such a sex determining system has evolved.

The sex of a reptile embryo partly results from the production of sex hormones during development, and one process to produce those hormones depends on the temperature of the embryo's environment. The production of sex hormones can result solely from genetics or from genetics in combination with the influence of environmental factors. In genotypic sex determination, also called genetic or chromosomal sex determination, an organism's genes determine which hormones are produced. Non-genetic sex determination occurs when the sex of an organism can be altered during a sensitive period of development due to external factors such as temperature, humidity, or social interactions. Temperature-dependent sex determination (TSD), where the temperature of the embryo's environment influences its sex development, is a widespread non-genetic process of sex determination among vertebrates, including reptiles. All crocodilians, most turtles, many fish, and some lizards exhibit TSD.

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.

For women with polyendocrine metabolic ovarian syndrome, or PMOS, combination oral contraceptives are a first-line treatment. PMOS is a reproductive hormonal disorder that affects roughly one in ten women of reproductive age and causes symptoms such as an irregular menstrual cycle and hyperandrogenism, or an excess of male-typical hormones called androgens. Combination oral contraceptives are medications containing a mix of synthetic female hormones that women often use as a means of birth control. In the 1970s, researchers found that the synthetic female hormones in combination oral contraceptives can reduce excess androgens in women experiencing PMOS. Several medical conferences in the 1990s and early 2000s created a diagnostic standard for PMOS, which led to an increase in diagnoses across the world and expanded the number of women who were receiving combined oral contraceptives for PMOS management. By relieving hyperandrogenism, combination oral contraceptives help women manage the symptoms of PMOS and reduce their risk of long-term health problems.