What Happens to Our Hormones After 35

Women, we have it tough. Once we hit our thirties, our hormones just can’t take it anymore. Balance becomes elusive. Mood swings become normal. And our family and friends want to avoid us 90 percent of the time. What gives? Are we doomed to the wild ride leading up to and through menopause?

Hormonal flux in perimenopause

Once we hit age 35 to 40, hormonal balance becomes elusive as estrogen, progesterone, testosterone, cortisol, thyroid, insulin, and leptin may become out of whack. It’s gradual for some and dramatic for others. But perimenopause and menopause need not be a tortuous slog through hormonal hell. Your body prefers to be in hormonal homeostasis, a state of equilibrium. A few tweaks are often all that’s needed to restore balance, whereas some of us need more support. I have strategies for both camps and everyone in between. My approach is the same, but duration may be longer if problems are more severe.

Perimenopause refers to the years of hormonal upheaval before your final menstrual period. It can begin in your midthirties or forties. However, perimenopause is a state of body and mind, not a chronological destination. It begins with dropping progesterone levels and ends with dropping estrogen levels in the year or two before your final period. For some women, it is a time when mood becomes unpredictable, weight climbs, and energy wanes—and most commonly, women experience a conflation of all three.

Women in perimenopause experience low progesterone as anxiety, sleep disruption, night sweats, heavier and shortened menstrual cycles—and fret over work and field trip permission slips in the middle of the night. Low estrogen may add mild depression to the mix, along with wrinkles, poor memory, hot flashes/night sweats, vaginal dryness, droopy boobs, and achy joints, more sun damage especially on the chest and shoulders. In your forties, gene variants like the short serotonin transporter gene (5-HTTLPR, or SLC6A4) can cause you to feel more stress, anxiety, and depression as estrogen drops. (Read more in my first book, The Hormone Cure, pages 62-63.)

Women in menopause commonly have low cortisol during the day (which makes them feel tired) and high cortisol at night, which makes them worry about everything from the stock market to whether their children finding their dream job and mate.

At any time, a woman can experience low thyroid function, but it’s higher after age fifty. Symptoms include lethargy, weight gain, loss of the outer third of the eyebrows, dry skin, dry strawlike hair that tangles easily, thin/brittle fingernails, fluid retention, high cholesterol, constipation, decreased sweating, cold hands and feet, cold sensitivity (i.e., skiing in Vail sounds miserable but a trip to Hawaii is just right).

Testosterone starts declining 1-2 percent per year starting in your thirties, and it leads to decreased confidence; feelings of helplessness; low or no sex drive; loss of muscle mass or less of a muscle response to resistance training; and loss of pubic hair and clitoral size. No bueno!

What else typically comes into play? Gut health, emotional factors?

Many women in their forties and fifties reach a point of reckoning and can no longer tolerate toxic or codependent relationships—or even their friendly neighbors who now just seem annoying and nosy.  Since hormones drive what you’re interested in, there’s certainly a hormonal component in the shift from the reproductive years to perimenopause. In your reproductive years, hormones fluctuate predictably every day and you accommodate other people’s needs, often at the expense of your own, and roll with the punches. In perimenopause, estrogen fluctuates wildly, you care less about pleasing others, and you become more comfortable with who you are. You speak your truth and stand your ground. (It happens earlier for some wise women, but for me, it began around forty-five.) Dr. Christiane Northrup first spoke about this, about how you pierce the hormonal veil starting in your forties and move into what I would call your wiser, more resourced, grounded years with greater faith in yourself and personal power.

Gut health also comes into play, and it’s bidirectional: your gut controls your hormone levels and your hormones strongly influence your gut function. The gut/brain axis puts your gut function at the center of any mood, weight, and energy issue that a woman faces. For example, excess stress and cortisol pokes holes in the gut, leading to symptoms like constipation, gas, bloating, loose stool, diarrhea and making you feel more tired and foggy. Nutrient deficiencies can show up, leading to moodiness, weight gain, even autoimmunity like Hashimoto’s thyroiditis, the primary reason for hypothyroidism. Beyond that, high perceived stress strongly affects the control system of most hormones, which is the brain/body system known as the hypothalamic-pituitary-adrenal-thyroid-gonadal (HPATG) axis. It’s a mouthful, but when a woman comes to my functional medicine office asking me to just write a prescription for bioidentical hormones so she can feel like her old self again, we have to look upstream at why her hormones are out of whack, and 99 percent of the time, the HPATG is in disarray. That’s the primary reason for hormone imbalance: wayward feedback loops in her control system. And fixing it begins with unlocking the most important hormone first, cortisol. Nearly all other hormones depend on it.

Unlocking cortisol isn’t a matter of meditating more or better (although that helps), but it requires measuring your cortisol (I prefer dried urine, at four points during the day) and how your body metabolizes it. This wear-and-tear hormone is in charge of blood sugar, blood pressure, gut, and immunity, so the cortisol unlock involves extensive lifestyle medicine adjustments, personalized for your life situation and root cause. A forty-seven-year-old runner who sleeps six hours per night, travels 50 percent of the time, and has high cortisol and low progesterone, might need more vitamin Bs, vitamin C, magnesium, adaptive exercise (yoga, Pilates), and maybe a botanical like chasteberry for progesterone, and Cortisol Manager to help her sleep. An overweight forty-two-year-old with carb cravings, weight loss resistance, and gas might need gut and blood testing, a detox, and a carb blocker. So the approach involves an integrated model of biology, psychosocial context, hormones, gut health, cell energy, and even genetic study.

If I had to make a list of the primary causes of hormone imbalance often overlooked by conventional physicians, they are:

• Aging
• Genetics
• Pregnancy and post-partum (you can have problems for up to eighteen years!)
• Inadequate nutrients (poor diet)
• Poor lifestyle choices like too much travel, bingeing on the wrong foods/drinks, skimping on sleep
• Toxic relationships, overextending yourself
• Toxic exposures, especially endocrine disruptors like bisphenol A, phthalates, lead, mercury, etc.
• Excess stress

A three-step protocol for resetting hormones

I apply what I call The Gottfried Protocol—my functional medicine approach to natural hormonal balance. It’s based on decades of research, my education at Harvard Medical School, my own experiences with hormonal imbalances, my belief in peer-reviewed, well-performed randomized trials to support my recommendations, and what I’ve learned from patients over the past twenty-plus years of practicing medicine.

When I dealt with my own hormone imbalances, my goal was to discover the root causes, to formulate a customized and rigorous fix, and to track my progress. I drew upon many sources, including traditional Chinese and Indian (Ayurvedic) medicine. In The Gottfried Protocol, I combine the latest medical advances and cutting-edge techniques with ancient treatments validated by modern research and scores of women in my practice.

Science has proven that your genes control only about 10 to 15 percent of your biology. They are a blueprint only. As a general rule, your environment controls the remainder. A rather simple formula of nutrient-rich food, targeted supplements to address missing precursors, and lifestyle changes can keep your genes in “repair” mode. Even if you’re genetically programmed to develop depression or cancer, the way you eat, move, and supplement can alter how your genes express themselves. This fascinating field of epigenomics examines how genes are modified without changing the DNA sequence—that is, how a gene for obesity, for instance, is modified by eating nonstarchy vegetables versus cupcakes. Your genes are merely a template, so you can leverage epigenomics to overrule genetic predispositions.

Epigenomics is the foundation of The Gottfried Protocol. Creating a methodology to assess, support, and maintain hormonal balance for myself and my clients took more than ten years. I defined, tested, and refined a progressive, systematic three-step approach that is reproducible and proven.

No matter what the hormonal problem is, the solution starts with:

Step 1. Lifestyle design: food and nutraceuticals to fill in the missing precursors to proper brain-hormone communication, and targeted exercise

Step 2. Herbal therapies

Step 3. Bioidentical hormones

Most of my recommendations are available without prescription. When women put an earnest effort into Step 1 of The Gottfried Protocol, they find most of their symptoms of hormone imbalance disappear. If they don’t, we shift to Step 2—proven botanical therapies. After completing Steps 1 and 2, few women need bioidentical hormones (Step 3), but for those who do, the doses and duration of treatment are often lower than if they’d skipped the lifestyle design and herbal therapies.

Sometimes only a small adjustment creates big changes. I love it when a patient realizes that she can alter her presumed life sentence of low sex drive with a particular form of meditation (like OM), a natural plant-based supplement like phosphatidylserine, and a maca smoothie.

What are specific symptoms of perimenopause?

Here is my official quiz from The Hormone Cure, pages 57-58, that might indicate you’re suffering from perimenopause, not that you’ve suddenly lost your mind.

Do you have, or have you experienced, in the past six months . . .

• Feeling less interested in daily chores (e.g., grocery shopping, laundry, dishes, and cooking)?
• A preference for introversion combined with wardrobe malfunction (reluctant to wear anything other than your yoga pants if you have to leave the house)?
• A need to wear stretchy pants (yoga leggings win again!) to make room for the roll around your waist, which seemed to arrive overnight?
• Emotional instability—for the first time in your life, you burst into tears at a moment’s notice, (even at work!)?
• Dissatisfaction with exercise (it doesn’t seem to affect your weight anyway)?
• Feeling blah or reclusive; you can’t wait to extricate yourself from normal activities and retire for the evening?
• Poor sleep (indiscriminate debates and ruminations awakening you in the middle of the night)?
• Waking up so sweaty that you need to change your pj’s and sheets, and perhaps even your husband (or partner)?
• Crow’s feet and/or a permanently furrowed brow?
• Apathy for personal grooming (you really don’t care how attractive you look, unless forced by your job or seeing friends)?
• Feeling less gung-ho about parenting?
• An unpredictable menstrual period—spotting or flooding or some weird combination of the two?
• Sudden forgetfulness when walking into a room (knowing you had a purpose but searching for clues as to what it was)?
• Doubting your own instincts and insights?
• More frequent announcements to the family that “I’m going to take a nap now” or “Mom needs a time-out”?
• A preference for chocolate or a glass of wine over sex?
• A notion that Zoloft or a little Lexapro, maybe an Ambien, sounds increasingly appealing?
• An opinion that addressing your mood issues by giving up sugar, alcohol, and flour, taking various supplements, and hormonal tweaking sounds like way too much work?

If you answered “Yes, most of the time!” to those questions and you’re ages thirty-five to fifty-five, welcome to perimenopause. This means your ovaries have started to sputter and are no longer manufacturing the same, predictable, and consistent levels of the sex hormones—estrogen and progesterone—that they used to. To make matters worse, your brain is less responsive to the hormones your ovaries still do produce and the happy brain chemicals such as serotonin may head south. Some women sail through perimenopause with nary a worry; others believe they are going crazy. Both are a normal reaction to the midlife hormonal flux.

What should you consider before taking hormones? Who is this right for?

I have a food-first philosophy, so I prescribe lifestyle medicine prior to bioidentical hormone therapy. In perimenopause, I recommend The Hormone Reset Diet as a start. In our experience with 25,000 women, the Hormone Reset protocol resolves 80 percent of hormonal symptoms including decreased depression and loss of 2 inches of the waist (probably an insulin resetting effect) according to a quantitative pre- and post-survey. If it doesn’t address your concerns within 4-6 weeks, move onto proven botanicals like chasteberry for PMS, ashwagandha for sleep, or Lavela for anxiety. It takes 4 to 6 weeks to reach a new equilibrium with hormones, so be patient. If your symptoms persist, it’s reasonable to discuss next bioidentical hormones.

Before taking hormones, it’s important to consider genetic and environmental risks. I ask my patients about contraindications including blood clots, pregnancy, moderate to severe endometriosis, enlarging fibroids or associated with heavy bleeding, gallbladder disease, liver disease (because the liver processes estrogen and sends it to the gut via bile), unexplained vaginal bleeding, atypical hyperplasia of the breast, some types of estrogen-sensitive breast cancer, endometrial cancer, ovarian cancer. To look for genetic contraindications or further issues to discuss, I run two different genomic profiles: 23andme and the Genova Estrogenomic Profile to make sure they are a good candidate. This conversation should include extensive informed consent of risks, benefits, and alternatives, all in a non-rushed context, i.e., no hand on the door.

It may sound like an obstacle course that few complete, but many of my patients safely choose bioidentical hormone therapy. Often it’s a quality of life decision, or a commitment for 3 to 6 months followed by a reevaluation. But when they’ve done Step 1 and 2 of The Gottfried Protocol, I find that my patients need the lowest doses and shortest durations, making the risk lower. I negotiate with my patients every 3 to 12 months for whether the benefits outweigh the benefits, and stop most treatment by 10 years post menopause (around age 60 to 65).

To be complete, risks include a greater chance of blood clots (venous thromboembolism), heart disease, stroke, gallbladder disease, and possibly breast cancer and dementia. Benefits include better mood and sleep, improvement in hot flashes and night sweats, lower appetite, increased lean body mass, less anxiety, higher sex drive, fewer clinical bone fractures and possibly lower rates of colorectal cancer. Alternatives include lifestyle and herbal therapies discussed in The Hormone Cure.

So what’s with bioidentical vs non-bioidentical hormones?

Why shouldn’t women consider replacing the hormones their bodies are missing, especially if their quality of life is miserable and they are good candidates for a safe experience?

There’s a popular movement to favor bioidentical hormones over synthetic hormones. Bioidentical hormones are exact replicas of the hormones your body makes during your fertile years, including estradiol and progesterone, which are the two hormones commonly referred to as “bioidenticals.” Synthetic hormones have a different chemical structure, which allows them to be patented by pharmaceutical companies. It’s important to recognize that bio- identical hormones include both U.S. Food and Drug Administration (FDA)–approved forms as well as non-FDA–approved forms made by compounding pharmacies, such as bi-est, which contains both estradiol and estriol.

Some alternative providers insist that bioidenticals solve every problem a menopausal woman has and are vastly superior to synthetic and animal-derived counterparts. Academic and mainstream thought leaders think you’re being taken for a ride. Where’s the truth? I suspect it’s somewhere in the middle. When I counsel a woman about taking hormone therapy, I recommend bioidentical estrogen and progesterone, including transdermal estradiol and oral progesterone, but with an important caveat: I assume that the risks of bioidentical hormone therapy are the same as synthetic until proven otherwise.

Overall, compounded bioidentical hormones often lack the regulatory oversight and rigorous testing that I believe women deserve. Based on current data, I prefer to prescribe FDA-approved forms of bioidentical hormones, particularly the estradiol skin patch and oral micronized progesterone (Prometrium) pills.

Bioidentical progesterone

Some women are at the point in their ovarian lives where an herb like chasteberry isn’t an option: because they are in late perimenopause or menopause, their ovaries can no longer respond. Time for Plan B.

For a woman with perimenopausal symptoms of shorter cycles, heavier bleeding, or difficulty sleeping, I prescribe bioidentical progesterone. You could start with a small dose of progesterone cream. Bioidentical progesterone is biochemically the same as the progesterone you make in your ovaries. In most over-the-counter creams, 20 mg equals about 1⁄4 teaspoon. Rubbing 1⁄4 teaspoon (about the size of a dime) into your arms where they’re hairless and the skin is thin, for fourteen to twenty-five nights per month, is often enough to relieve the symptoms of low progesterone.

There are several randomized trials demonstrating the efficacy of progesterone cream for women with symptoms of low progesterone, such as hot flashes. One examined a dose of 20 mg a day, and when it came to hot flashes, 83 percent in the cream group experienced fewer flashes (versus 19 percent in the placebo group), but several of the women experienced vaginal bleeding. If you have bleeding, this must be investigated immediately. Another trial looked at a dosage of 32 mg per day, and found that the progesterone cream raised serum levels but did not change hot flashes, mood, or sexual drive. One trial of progesterone cream at various doses showed no change in hot flashes—this time using progesterone cream at doses of 60, 40, 20, and 5 mg or placebo. Another review found no benefit, so the data are not concordant. It’s possible that the different formulations of progesterone cream are responsible for the inconsistent results; anecdotally, many of my patients find it to be helpful.

Bioidentical estrogen

I am confident recommending estradiol patches to appropriate patients, provided they do not have issues that make them unsafe, such as a history of blood clots or if they are ten years past menopause (beyond ten years from menopause, risk of heart disease rises—see above). Because these patches are approved by the FDA, there is excellent regulatory oversight. Examples are Vivelle Dot and Climara, taken at the lowest doses that relieve symptoms. I’ve found that, for most of my patients, doses of 0.025 mg or 0.0375 mg work effectively.

Estrogen’s ability to raise serotonin, which is associated with improved mood, sleep, and appetite, is well proven. At the latter half of perimenopause, which normally begins around age forty-three to forty-seven, estrogen withdraws from the daily hormonal menu. Many women find that estrogen withdrawal causes serious mood changes, which may relate to genetic vulnerability combined with environmental factors, the so-called GxE interface. Data from a randomized trial that examined perimenopausal women aged forty to fifty-five who had either major or minor depression showed that the estrogen patch caused remission of symptoms in 68 percent of women assigned to the patch, and 20 percent in the placebo group. In short, estrogen has an antidepressant role, particularly in mood disorders affecting women over forty.

Any woman with a uterus who takes systemic estrogen of any type, such as a cream, patch, or pill, must counterbalance the estrogen with progesterone, delivered orally as a pill, to prevent buildup of excess tissue in the uterine lining, which may turn into precancer or cancer. I believe in the lowest possible doses of FDA-approved and regulated transdermal estrogen balanced with oral progesterone, if you have a uterus.

Women may have more hormonal issues and related conditions—anxiety, Hashimoto’s, depression, autoimmune disease—but that means we need a way to understand the root causes and then solve them. Awareness, acceptance, action!