This week saw news on the controversial topic of gender-affirming care, with a group of five youths ages 9 to 16 suing the state of Louisiana for enacting a bill banning such health care for minors. Such bans exist in some form in 20 other states, with similar legal challenges currently active in many regions.

Here at DH3, we will cover some of the topics touching such cases, but given our focus on getting to the roots of health topics, we’re going to start with a contextual dive about hormones.

This is a foundational post that will feed into interesting questions in future posts like:

• Why do men need estrogen, and women need testosterone (you read that right)?
• What are hormone disruptors and how might they be changing pregnancies (and miscarriages), puberty, intelligence, and more.
• Is soy really that bad for you? What about lavender?
• What treatments are used for hormone therapy, and how can they help many people?
• What are puberty blockers, and are they reversible?

A complex and mysterious system

When I was in medical school, there were a few fields most of us future doctors knew were super complicated, and a few were just plain mysterious. Neurology is complicated. The average human brain has about 86 billion neurons and as many support cells for the neurons. Nephrology is complicated. It takes a human computer to understand the ions and channels needed to make pee right.

Endocrinology is just plain mysterious. We have identified over 200 different types of hormones (what!). We even call some substances hormones only if they’re in specific body areas. Finally, all hormones get jumbled up in our bloodstream, and we cannot precisely track how much is getting to their end destinations (receptors) and affecting us in a certain way.

The information system of the body

Endocrine - “endo” is Greek for “within,” and “crinis” is Greek for “to secrete.” This esoteric term refers to a system in which hormones are secreted within the body (directly into the bloodstream) by the glands of the endocrine system. I'm half convinced that this specialty is as unknown as it is because it isn't simply called the "hormone system."

We also have a relatively unglamorous exocrine system (no doctors specializing in this one). This system involves glands that secrete substances through ducts to the outside of the body or into internal cavities (like the gut). This system includes sweat, salivary, and digestive enzyme-producing glands. The practice of dealing with this system gets divvied up between dermatologists (skin includes the sweat glands), otolaryngologists (AKA ear, nose, and throat doctors who care about salivary glands), and gastroenterologists (dealing with all gut things from mouth to butt).

What are hormones?

We’ve all heard it, said it, or felt it. Hormones have taken a colloquial character in society without the vast majority of us using the term with any precision. What we vaguely understand as true is that they’re vitally important for functions including our emotions.

Hormones are the body’s chemical messengers, traveling in your bloodstream to tissues or organs. At its most basic definition, a hormone is a molecule that allows Cell A to tell Cell B to do something (the body is made out of > 38 trillion cells that need to communicate with one another!).

These messengers - hormones - are less like text messages and more like messenger pigeons. (This is in contrast to electrical signals used by organs like the heart or neurotransmitter signals used by the brain, both of which are nearly instantaneous in speed.) Hormones work slowly over time and affect many different processes, including growth and development, metabolism, sexual function, reproduction, and mood. Altering them through medication thus also acts rather slowly.

Balancing on a tightrope

Hormones are crucial for our daily well-being. They play a pivotal role in maintaining homeostasis, regulating energy levels, and influencing our emotional states. A slight imbalance can have significant effects, so understanding hormones is critical.

Common Functions of Hormones

Below are some quick categories of functions hormones help out with.

• Growth and Development: Hormones like growth hormone, thyroid hormone, and sex hormones play a significant role in how we grow and develop from infancy into adulthood. A big upcoming topic will be the use of hormones in supplementation (such as testosterone and peptide therapies) as well as the role of endocrine disruptors in causing a myriad of issues from infertility to anatomical changes.

• Metabolism: Hormones such as insulin and glucagon regulate how we utilize energy, impacting our blood sugar levels and overall energy. We will definitely cover insulin resistance and the new hotness in pharmacology (GLP-1 agonists and adjacent mechanism drugs, known by brand names Ozempic, Mounjaro, Wegovy, Zepbound, and more).

• Reproduction: Estrogen, progesterone, and testosterone are key players in reproductive health and sexual function. As mentioned above, there are mysteries about reproductive hormones we are learning more about and will cover in great depth. In addition to endocrine disruptors, we will do deep dives into topics like assisted reproductive technologies like IVF. We’ll also cover growing diagnoses like PCOS that affect not only fertility but have far-reaching impacts on weight, metabolism, skin health, and more. Finally, this is the big category that impacts gender-affirming care.

• Stress Response: Cortisol, known as the ‘stress hormone,’ helps our bodies respond to stressful situations. There is a great deal of concern about what chronic stress is doing to humans. We’ll undoubtedly have a great post or two covering stress, its outcomes, and evidence-based methods for managing it.

Covering our Ts and Es

As we discussed, there are a ton of hormones to cover, but perhaps none more hotly discussed than our primary sex hormones.

Testosterone

Androgens (the most important of which is testosterone) are considered masculine hormones but are vital in both biological sexes.

Some other androgens you will come across are important to distinguish if you’re considering testosterone-modifying treatments (such as for T supplementation, hair loss prevention, and so forth).

• Androstenedione
• Dehydroepiandrosterone (DHEA)
• DHEA-sulfate (DHEA-S)
• Dihydrotestosterone (DHT)

Common androgen-related treatments you might come across include the following:

• Spironolactone - this is a blood pressure, PCOS, and acne medication that blocks androgen receptors. Its use for the heart (such as in heart failure and hypertension) is due to its function as a diuretic (makes you urinate out excess fluid). Its use for skin-related concerns like acne, seborrhea, and hirsutism (masculine hair growth) is due to his androgenic blocking properties. It can be used in females who desire to prevent female pattern hair loss, but is less useful for male pattern hair loss in males since this latter process is governed more by DHT. Not to mention, spironolactone can lead to feminizing effects like gynecomastia (growth of breast tissue in males).
• Finasteride and Dutasteride - these are 5-alpha reductase inhibitors that have grown in popularity in recent years due to companies like Ro and Hims promoting them as hair loss drugs. They work by blocking…5-alpha reductase…which is an enzyme that converts testosterone to DHT. DHT is responsible for male pattern balding and benign prostatic hyperplasia, so you can kill two birds with one stone with these relatively affordable medications.

Fun fact: Women secrete greater amounts of androgen than of estrogen. The testes secrete androgens in males, and the ovaries secrete androgens in females.

Estrogens

Estrogens are divided up into three main types: estrone, estradiol, estriol, and estetrol. They are named for the number of hydroxyl groups they contain. Interestingly, the more hydroxyl groups doesn’t correlate with strength (E2 is the most potent type).

Estrogens are synthesized from cholesterol and secreted from the gonads (testes and ovaries), and a lesser amount can be converted from adrenal androgens in adipose tissue (fat). This is why males with more adipose have a higher chance of developing gynecomastia.

1. Estrone (AKA E1) is a weak type of estrogen that can be converted to estradiol. Its potency is estimated ot be 4% that of estradiol. It is sometimes used as a medication, such as for estrogen supplementation in menopause.
2. Estradiol (AKA E2) is the most important, potent, and prevalent in premenopausal women. It is responsible for development of breasts, widening of hips, and female fat distribution. It is important in non-sexual function for tissues like bone, fat, skin, liver, and the brain. It is also used in menopausal hormone therapy, and additionally in feminizing hormone therapy for transgender women.
   1. Fun fact: Males need estradiol too! It functions to prevent apoptosis (death) of sperm cells. It can also impact the tissues mentioned above, having an impact on skin, skeletal, circulatory, and cardiac health.
3. Estriol (AKA E3) is a weak estrogen that is present in detectable levels only in pregnant females. It is synthesized at high levels by the placenta. Its function is to be used by the fetus to produce sex hormones of its own. It can also be used in menopausal hormone therapy. Its potency is about 20% that of estradiol. The primary exciting use of estriol is as an anticancer medication since it blocks specific receptors where estradiol acts as an agonist (a method by which some breast cancer cells proliferate).
4. Estetrol (AKA E4) is an estrogen only produced by the fetus (in its liver). It can also be used as a medication, and a new oral contraceptive has been approved using estetrol as a component. It is also used for menopausal symptom treatment.

In addition to direct supplementation, estrogens are commonly used in oral contraceptives.

• Oral contraceptives (“birth control pills”) - these are typically combination pills of estrogen and progesterone that women take to prevent pregnancy. They can also be used to regulate menstrual cycles, mood, acne, and other cycle-related symptoms. OCPs work for these functions by blocking ovulation and maintaining a steady state of estrogen and progesterone throughout the month. Over 10M women in the US take OCPs, making them one of the most popular medications in current use.

Alright - that’s it for now! I wanted to give everyone a primer on hormones and this turned into a massive essay. We’ll come back to this topic time and again. Please send me feedback such as how I can make this more interesting for you!

Cheers to your health,

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Hillary Lin, MD

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