Let’s talk about sex ba-by! Or rather sex hormones (and you’re welcome for getting that old Salt-n-Pepa song stuck in your head!). There are three groups of sex hormones that are produced in the ovaries, testes, and adrenal gland: The Progestogens, the Androgens, and the Estrogens.
Cholesterol gets a bad wrap, but actually it is very important in our bodies: from cholesterol Progestogens are produced, which go through enzymatic reactions to make our Androgens and Estrogens.
While other hormones are involved in sex-related processes, such as the Luteinizing Hormones (LH), Follicle-Stimulating Hormone (FSH), and Gonadotropin-Releasing Hormone (GnRH), these are not considered sex hormones. These are polar polypeptide (protein) hormones, whereas sex hormones are nonpolar steroid hormones.
When people hear steroids they often think of big bodybuilders or athletes who use steroids to bulk up or give them a competitive edge, but the term “steroid”, in fact, refers to the chemical structure of the hormone. Steroids are, by definition, nonpolar organic compounds with four ring structures (3 six-carbon structures and 1 five-carbon structure).
Here we have the big three: Estradiol, Progesterone, and Testosterone. They are the major hormones for each of the three groups, and you can see they all share that basic structure of four hexagonal rings and one pentagonal ring. This structure exists in ALL of your sex hormones.
What gives each hormone its special capabilities to cause men to have hairy chests and deep voices, and women to have menstrual cycles and breasts are those components that stick off the main four-ring structure, called “functional groups”. Because these groups vary on each hormone, each hormone has its own unique chemical “identity” that the body’s receptors recognize. When the receptors and the hormone interact, the cascade of physical and chemical changes occur in the body to keep and maintain secondary sex characteristics of males and females, regulate menses, and a myriad of other functions.
Don’t worry, I won’t make you sit through an Organic Chemistry lecture; I did that so you don’t have to. However I do think it helps to see the hormones and their similarities and differences. When you have an image in your mind of how they look, they can become less esoteric or mysterious and more tangible to the everyday person.
Progestogens
We’ll start with first things first. Progestogens are so named because of their role in pregnancy and fetal development, hence they are progestational, “pro” + “gestation.” There are several hormones that exist in the group, but the major and most important is the hormone Progesterone, whose name is derived from the ketone group depicted above; “progester” + “one”.
The levels of progesterone rise and fall during the menstrual cycle, peaking just after ovulation in preparation for supporting the corpus luteum in case there is a fertilized egg that will implant itself into the uterine lining. If pregnancy doesn’t occur, progesterone levels drop and menstruation starts.
ESTROGENS
When we speak of estrogen we often do so rather generically, though we are unknowingly referring to a specific type of estrogen. Generally we are actually talking about Estradiol, the major female sex hormone.
There are four types of estrogens that can be found: Estrone (the primary estrogen during menopause), Estradiol (the dominant estrogen during a woman’s reproductive years), Estriol (synthesized by the placenta during pregnancy), and Estetrol (found only during pregnancy). Often you may read there are only three endogenous estrogens – that’s because Estetrol is, in fact, made by the fetal liver exclusively. Your baby actually makes this estrogen, and then it circulates in your bloodstream! And you did the same thing to your mother!
In the figure you can see the differences between the four different estrogens:
Estrogens were the first of the steroid hormones to be isolated; specifically Estrone was the very first in the late 1920s. The name came from the term “estrus,” the term for the menstrual cycle in animals, combined with the “-one” suffix from the ketone functional group (shown with the blue arrow). Estriol and Estradiol were discovered shortly thereafter; Estetrol wasn’t discovered until the 1960s.
The names may seem confusing at first, but in reality they are simply describing the functional groups on the main four-ring structure. In chemistry, hydroxy groups, the –OH you see indicated by blue arrows on the E2, E3, and E4 images, have the suffix “-ol.” This is where alcohol also gets its name. Also, chemistry nomenclature typically uses the Greek numeral prefixes: mono-, di-, tri-, tetra-, penta-, hexa- (1, 2, 3, 4, 5, and 6, respectively). Therefore, Estradiol really is “estra-di-ol,” or an “an estrogen hormone with two hydroxy groups,” but that is just a mouthful! Similarly, “estra-tri-ol” and “estra-tetra-ol” became Estriol and Estetrol because their respective three and four hydroxy groups.
See! Now when you hear their names used in hormone news articles, you will be able to understand and picture them in your head.
So what do these estrogens do individually in the body?
Estrone (E1) is the dominant estrogen during menopause. It gets a pretty bad reputation, though, because it is considered ‘pro-carcinogenic,’ leading many to call it an “unhealthy estrogen,” when in reality it has good roles, too. It is important to the health of your heart and brain – it helps protect your brain after a stroke or other trauma, and it protects the lining of your blood vessels and helps to keep them dilated.1
Your body makes it throughout your life, but when menopause hits, your Estradiol levels plummet, leaving Estrone as the prominent estrogen. Compare the levels of Estrone to Estradiol in the body throughout development, into menopause. (The levels for males are included to show that, while estrogens are considered female hormones, it’s important to remember they are not exclusively found in women.)2
Data Source: Treatment for high estrogen
Estradiol (E2) is the major female sex hormone throughout your reproductive years, responsible for developing female genitalia and maintaining the secondary female characteristics, including narrower shoulders, less body hair, breasts, and female fat distribution and wider hips (cue collective groan here). It also is responsible for regulating menstrual cycles. Though generally found at levels higher than other estrogens, it oscillates during the month, rising and falling twice - peaking right before ovulation and then drops very low, then peaks again during the luteal phase (though not as high), and then drops very low again until after your period.3 Even if there is slightly more Estrone in your body than estradiol, it is important to remember that estradiol is actually a more powerful estrogen.
While made in the ovaries, testes, and adrenal glands, it is also made in fat, the liver, breasts, and brain. Besides its reproductive roles, it is also very important to maintaining bone density, skin elasticity and firmness, brain patterning, and plays a role in creating certain liver proteins. So it takes a pretty big toll on the body when the levels of estradiol become depleted as we see occur after menopause.
Estriol (E3) is made in very high quantities by the placenta during pregnancy, before and after which levels are nearly undetectable. Comparatively, both Estrone and Estradiol increase 100-fold during pregnancy, where as Estriol actually circulates at levels 1000-fold greater.4 A vast majority of this estrogen is secreted by the placenta, made from cholesterol provided by the mother. 5 The role of this estrogen in development is still not well understood.
The final estrogen, Estetrol (E4), is another pregnancy-only estrogen, but it very unique in that it is produced in the liver of the baby inside the womb. Like estriol, it is a very weak estrogen. Its function is also not very well understood. Some have suggested it may have a protective effect from maternal estrogens, and/or its function may be limited to the area where it is produced.6
ANDROGENS
Androgens, from the “andro-,“ the Greek word for ‘man’, are the group of hormones responsible for typical physical development of male characteristics. There are three main androgens that occur in the body: Testosterone, Dihydrotestosterone (DHT), and Androstenedione.
Looking at the picture, you can see the groups that give each androgen its unique “identity.” Dihydrotestosterone is so named because it has two more hydrogens than Testosterone (they’re generally not drawn in organic diagrams; in case you are wondering, they are located where I have noted the double bod has changed to a single bond. They’re there, just invisible!). Androstenedione’s name, on the other hand, has “di-one” at the end because it has two ketone functional groups attached to it.
TESTOSTERONE
Testosterone is the primary male sex hormone and plays a major role in development of the testes and prostate, spermatogenesis, and increased sex drive. Because it is an anabolic steroid, it is also key to developing the increased bone and muscle mass that are characteristic of the male physique. It is also crucial to other secondary male characteristics including voice deepening and increased sebum production, and consequently acne as well.
But it’s not just all about the external characteristics – testosterone is also involved in masculinization of brain patterning; testosterone in the brain is converted to estradiol which then affects the neuronal development.
In women testosterone is made primarily by the ovaries, though in much smaller quantities than that which is found in males. While it does contribute to female sexual arousal, too much testosterone in women leads to excess hair, decreased fertility, and a plethora of other issues.7 High levels of testosterone can be seen in women with Polycystic Ovarian Syndrome (PCOS).
DIHYDROTESTOSTERONE
Because we know so much about Testosterone, we might think it is the most powerful of the androgens, but we would be wrong. Despite the fact testosterone is the most prolific androgen in the male body, DHT is actually the most potent of the androgens. However, in the prostate DHT levels are overwhelmingly greater than that of Testosterone. This is because the majority of Testosterone in the prostate gland is converted to DHT – one of DHT’s roles is the maintenance of the prostate gland, so a lot of DHT is needed in that area.
While DHT is responsible for the maturation of the penis and scrotum, it is unfortunately a responsible party in male pattern baldness and prostate cancer. In relation to DHT’s role in male genitalia maturation, there is a subset of the population in the Dominican Republic in which children who appeared to be girls become boys at puberty.8 These children, called guevedoces, have a genetic mutation in the enzyme 5α-reductase, which is responsible for converting Testosterone into DHT. Because they don’t have enough DHT in their body early in development, they often don’t have descended testes or a visible penis. The name Guevedoces comes from the slang term for testicles gueves, and doces meaning 12, the age at which they often start hitting puberty. 9 Because of the flood of Testosterone and DHT that is created during puberty, it overwhelms their bodies and they actually grow their male genitalia at puberty. A painfully scary thought, one can imagine!
ANDROSTENEDIONE
The final androgen, Androstenedione, is a relatively weak androgen, and it acts more like a prohormone because it can be used for making both Testosterone and Estrone. The levels for this androgen begin to increase around 6-8 years old in developing children, though the impetus behind this is not well understood. It is hypothesized that it is involved in social/cultural/ecological learning and, perhaps relatedly, may play a role in competition and aggression in boys.10
So that’s a little peak under the microscope. Hopefully when you read articles discussing “estrogens” or “androgens,” you can understand them better and start to understand what parts of your body these hormones can affect.
1 Estrone - A Most Maligned Estrogen
2 Signs and Symptoms of High Estrogen - HealthLine
3 Reed BG, Carr BR. The Normal Menstrual Cycle and the Control of Ovulation. 2018 Aug 5. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279054/
4 Susan Blackburn (14 April 2014). Maternal, Fetal, & Neonatal Physiology. Elsevier Health Sciences. pp. 39, 93. ISBN 978-0-323-29296-2
5 Falah, N., Torday, J., Quinney, S. K., & Haas, D. M. (2015). Estriol review: Clinical applications and potential biomedical importance. Clinical Research and Trials,1(2). doi:10.15761/crt.1000109
6 Wardell, S. E., Mcdonnell, D. P., & Nelson, E. R. (2013). Regulation of Bone Cell Function by Estrogens. Osteoporosis,329-344. doi:10.1016/b978-0-12-415853-5.00014-5
7 Traish AM, Kim N, Min K, Munarriz R, Goldstein I (Apr 2002). “Role of androgens in female genital sexual arousal: receptor expression, structure, and function”. Fertility and Sterility. 77 Suppl 4: S11–8. doi:10.1016/s0015-0282(02)02978-3. PMID 12007897.
8 The extraordinary case of the Guevedoces - BBC Magazine
9 Bainbridge, D. (2003). Making babies: The science of pregnancy. Cambridge, MA: Harvard University Press.
10 Gray PB, McHale TS, Carré JM (May 2017). “A review of human male field studies of hormones and behavioral reproductive effort”. Hormones and Behavior. 91: 52–67. doi:10.1016/j.yhbeh.2016.07.004. PMID 27449532.
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