Chemicals in Concert

From puberty to PMS, the term hormones gets bandied about often when we’re feeling out of tune, but how well do we really understand the endocrine system from which these chemical notes flow? Read on to hear more about how the body’s messengers sync up to keep our internal rhythms humming along

WRITTEN BY Lauren B. Johnson
PHOTOGRAPHS BY (brain) Metamorworks; (Dr. Yacoub) Niki Nero & (Katrina Nell & Jerry Holst) Scott Henderson; (Dr. Eustis) courtesy of Dr. Eustis

In the same way an orchestra performs in concert, the endocrine system works together to harmonize the body’s internal functions. With the pituitary acting as the conductor, our glands generate hormones to keep everything from hunger to heart rate in tune and on tempo. As we age, however, key changes to this endocrine symphony—notably the reproductive system—can leave us feeling out of sync. (Cue Menopause The Musical.) Roper St. Francis Healthcare affiliated gynecologist Dr. Elaine Eustis and endocrinologist Dr. Sherif Yacoub help explain the dynamics of these all-important chemical messengers, as well as the treatments that doctors can use to fine tune their performance.

Chemical Messengers

Hormones can be thought of as messengers responsible for telling parts of the body that it’s time for action. The endocrine system produces these chemical cues in glands all over the body and then transmits them via the bloodstream to our organs and tissues to control functions such as reproduction, metabolism, growth, development and behavior. Once there, the hormones bind to cell receptors, which are like designated parking places, and signal the body to react per the memo.

A simple example of this messenger system can be found in a rumbling tummy. An empty stomach secretes ghrelin into the bloodstream. When this “hunger hormone” reaches the hypothalamus (our endocrine system’s main switchboard), it informs the brain that food is needed. Ghrelin also tells the pituitary gland to release growth hormone, which breaks down fat tissue and builds up muscle. Once fed, the stomach slows its production of ghrelin.

From appetite and energy to stress and blood pressure, hormones help our bodies stabilize internal conditions in order to survive. “Many of the hormones in the body are controlled through a complex releasing system that begins in the brain,” says Dr. Eustis. At the helm of the endocrine system, the pituitary gland sends and receives signals from all other glands, including the thyroid, pancreas, adrenal glands and gonads.

His and hers hormones function similarly in the brain but diverge when they reach the gonads. The pituitary gland sends luteinizing hormone (LH) and follicle-stimulating hormone (FSH), collectively called gonadotropins, to stimulate the secretion of sex hormones in the testes and ovaries. Men and women both release the female hormone estrogen and the male hormone testosterone, though in vastly different amounts. “The testosterone level in men is far greater than estrogen and vice versa in women, usually by a factor of 10 to one,” explains Dr. Yacoub. These hormones are responsible for the reproductive system as well as secondary sex characteristics like breast development, facial hair and body mass. Part of a group of male sex hormones known as androgens, testosterone affects muscle formation, stamina, hair distribution, libido and energy levels. Estrogen contributes to cognitive function, bone health, metabolic processes and libido.

The Swing of Things

As we age, hormones shift according to the body’s needs. “Aging is a process of adaptation,” says Dr. Yacoub. Growth hormone, for example, is heightened during childhood and surges at puberty but declines as we get older. By the age of 55, our growth hormone levels drop by about one-third what they measured during early adulthood. This decrease can negatively impact muscle strength, energy levels and fat distribution. “But the decrease in growth hormone isn’t necessarily bad,” explains Dr. Yacoub, pointing out that growth hormones follow many of the same pathways used in cancer cell growth and insulin signaling. “If we had as high a level of growth hormone in older age as we did in our teens, we would see a massive increase in cases of cancers and diabetes.”

Sex hormone production also fluctuates as we get older. During transitional phases such as puberty, pregnancy and middle age, the pituitary gland floods the gonads with LH and FSH. Beginning in girls as early as age nine and in boys around age 10, a dramatic boost of sex hormones signals the start of adolescence and prompts the maturation of reproductive organs. “Our hormones settle into an optimal range during our 20s and 30s,” says Dr. Eustis.
In our 40s, production of the dominant sex hormone begins decreasing. While this drop occurs in both men and women, the change manifests in dramatically different ways. “For men, the decrease in testosterone usually isn’t sudden,” says Dr. Yacoub. Conversely, women undergo a rapid decline in estrogen production, a process known as menopause.

“The Change”

Menopause marks the cessation of hormone production by the ovaries and, thus, the end of a woman’s menstrual cycle. “The technical definition of menopause is when a woman goes a year without a period,” says Dr. Eustis, a certified menopause specialist with the North American Menopause Society. While the average age for this shift is 51.7, the symptoms associated with the decline in estrogen and progesterone can begin several years before a woman’s final period (a time known as perimenopause) and last several years after.

In their early to mid 40s, women experience a hormonal turbulence similar to that of the teen years. “As the ovaries begin losing function, they stop signaling the brain,” explains Dr. Eustis. “In response, the pituitary gland cranks out more FSH to rev the ovaries back up.” The strategy works, but only for a few years.

“Perimenopause is a very under-appreciated phase,” continues the doctor. “Super high estrogen levels can wreak havoc on a woman’s emotions.” Symptoms of this natural transition include heavier and more frequent menstrual cycles, worsening PMS and mood swings, anxiety, depression, insomnia, weight gain and low sex drive.

When the ovaries finally stop responding to the pituitary’s pumped-up FSH signals, menopause begins. Without estrogen or progesterone production, the body becomes subject to hot flashes, night sweats, vaginal dryness, foggy thinking and memory loss on top of the symptoms that may have begun during perimenopause.

“Patients often ask me, ‘How long does menopause last?’ The fact is, menopause lasts the rest of your life, because ovarian function doesn’t return. But the symptoms of menopause usually only last three to 10 years after your final period,” reassures Dr. Eustis. In 85 to 90 percent of women, symptoms wane by the late 50s. “Of course, there are exceptions—some women don’t have any trouble while others continue to get hot flashes into their 80s.”

Whether or not a woman’s periods have stopped, if she’s vexed by overwhelming hot flashes, night sweats, insomnia or mood changes, relief can be found with hormone replacement therapy (HRT). Just as the name indicates, this form of prescription treatment involves replacing rapidly dropping estrogen, as well as progesterone in some cases, to alleviate symptoms. “The type of hormones used will vary from patient to patient based on her goals, age, symptoms and medical and family history,” says Dr. Eustis.

To determine the ideal hormone balance to reinstate a patient’s quality of life, a doctor uses a symptom questionnaire and a blood test. (The North American Menopause Society doesn’t recommend saliva tests, as they are costly and unreliable.) Given as pills, patches, gels and creams, HRT involves two categories of hormones: natural and synthetic. Often called bioidentical, plant-derived natural hormones molecularly match our own. Synthetics, on the other hand, are not identical to human hormones but can park in those hormone receptor spaces and produce the same effects. Compounding pharmacists may customize a hormone prescription, typically with bioidentical chemicals, if a satisfactory commercial blend is unavailable or too costly.

While certain combinations of hormones can present slightly increased risks of cancer and blood clots, patients who begin HRT before age 60 also gain greater protection of heart, bone and memory health. (Dr. Eustis points out that the risk of breast cancer from HRT is no more than that associated with drinking a glass of wine a day.) “The concept of ‘the lowest dose for the shortest period of time’ is outdated,” she emphasizes. “Instead, we aim for the appropriate dose, duration, regimen and route of administration.”

The Reality of Low-T

Unlike the rapid estrogen drop that women experience, testosterone levels in men diminish only by about one percent each year after age 40. While this gradual decline can result in muscle loss, fatigue and increased belly fat, “the natural decrease of testosterone shouldn’t really cause significant problems,” Dr. Yacoub says. He stresses that the male hormonal slide, sometimes referred to as andropause, is not analogous to menopause. “If testosterone levels drop enough to cause symptoms, then there is usually another underlying cause, such as excessive alcohol use or sleep apnea.” Only about one in 10 cases of low testosterone (low T) is the result of damage to the testicles; in the remaining nine cases, the pituitary gland doesn’t secrete enough testosterone.

Doctors often use a quantitative questionnaire such as the ADAM (Androgen Deficiency in the Aging Male) to identify excessively low testosterone. The weighted questions ask patients about decreased sex drive, erectile dysfunction, muscle strength, energy levels, fatigue and more. A morning blood test might also be used to measure hormone levels, since “testosterone levels peak in the morning and can go down by 30 to 50 percent during the course of the day,” explains Dr. Yacoub. “Checking testosterone levels in the afternoon can result in a false diagnosis of low T.”
While HRT can be used to treat low T, the doctor stresses the importance of understanding why testosterone levels are diminished before jumping straight into treatment. Taking a hormone replacement without addressing any underlying cause may bring testosterone levels back up, but symptoms won’t abate until the root of the problem is managed. An undiscovered issue also opens the door for bigger health problems. “The two factors I see most often are excessive drinking and obstructive sleep apnea, but low T can also be the result of pituitary tumors or brain trauma,” Dr. Yacoub says.

For a man who has pituitary or testicular damage and cannot secrete testosterone anymore, HRT is an appropriate course of action. “When giving testosterone, the goal is to restore normalcy rather than striving for industrial strength,” says Dr. Yacoub. Exceeding the recommended amounts of testosterone may negatively impact cholesterol, blood pressure and the cardiovascular system. Since the prostate feeds on this hormone, doctors will also closely monitor that gland. “As far as we know, testosterone treatment doesn’t cause normal tissue to become cancerous, but if a patient already has a small cancer in the prostate and takes testosterone, that spot will get larger.” He also notes that the body comes to rely on the cream or injection and loses its ability to naturally produce the hormone, another reason men should only use HRT when truly necessary.

Hormones in Harmony

Like that orchestral symphony in which the strings and woodwinds match the brass and percussion sections, our hormones work best when in balance, not higher or lower than their ideal range. “More isn’t necessarily better. There are optimal points for hormones at different times in both a man and woman’s life,” says Dr. Yacoub.

“A woman’s ovaries eventually stop working regardless of how healthy she is,” adds Dr. Eustis, “but those who eat a wholesome diet, maintain a good weight and exercise regularly tend to have fewer and milder menopausal symptoms.” A healthy diet marked by whole foods, lean proteins, low sugar and high-quality fats can help maintain that equilibrium. Regular exercise also works to regulate hormones like insulin, adrenaline and cortisol as well as muscle-maintaining hormones like testosterone. And physical activity works in concert with sleep quality, which has been shown to stabilize the hormones linked to energy, stress and growth. With a spotlight on smart lifestyle choices and HRT accompaniment when needed, we can set the stage for our chemical messengers to maintain the body’s complex internal melody.

The Flow Chart

A brief look at the hormonal shifts that take place during a woman’s menstrual cycle and pregnancy

Day 1: First day of her period

Days 1-14: Estrogen production gradually increases

Day 14 (ish): Ovulation occurs; estrogen levels spike and progesterone production begins

If conception does not occur:

Day 22: Progesterone levels peak

Days 23-28: Estrogen and progesterone gradually decline as the next period approaches, resulting in physical symptoms such as breast tenderness, headaches, bloating, depression and mood swings (PMS, for short)

If conception occurs:

Day 21: The body begins producing the pregnancy hormone human chorionic gonadotropin (hCG); levels of hCG double every two days during the first 10 weeks of pregnancy

Week 8: The placenta takes over progesterone production from the ovaries

Week 12: Estrogen and progesterone levels rise to nearly 1,000 times higher than their baseline

Birth: Estrogen and progesterone levels quickly plummet while prolactin and oxytocin levels surge

*While many other factors are also at play, the post-birth hormonal roller coaster can trigger postpartum depression in as many as 15% of women. If you find yourself feeling hopeless, crying easily or thinking about harming yourself or your baby, seek immediate help from your ob-gyn.

Parabens, Phthalates, and BPA, Oh My!

From pesticides and plastics to household cleaners and synthetic fragrances, there are hundreds of chemicals in our water, air, soil and food. When these endocrine disrupters get into our bodies, they can block or mimic our
natural hormones and undermine development, reproduction, metabolism and immune systems. “You can’t live in this country and not be exposed to endocrine disrupters, but there are basic things you can do to reduce your exposure,” says Dr. Eustis.

• Wash produce thoroughly
• Buy organic when possible
• Choose products marked as BPA-free or paraben-free
• Opt for stainless-steel or glass food and beverage containers
• Avoid microwaving plastic and Styrofoam containers
• Use fragrance-free products
• Launder new clothing and bedding before use