A functional medicine-based approach to hormone replacement therapy

The hormonal changes that occur during menopause bring about some significant changes for most women. As the reproductive cycle comes to a close, the production of many important hormones decreases greatly, which can cause a myriad of problems. Women may experience a variety of unpleasant symptoms, from hot flashes and weight gain all the way to increased UTIs and even cognitive decline. Many of these problems can be traced back to the changes in hormone production. Most women just never feel the same and struggle to feel like themselves again.

Symptoms of menopause

• Increased UTIs
• Vaginal dryness, itchiness, and pain
• Increased yeast infections
• Headaches
• Mood changes
• Memory loss
• Depression
• Anxiety
• Hot flashes
• Night sweats
• Joint pain
• Weight gain
• Sleep disturbances

Why can’t women just take estrogen?

We’ve talked at length about estrogen and the effects of its decreased levels on women. So why don’t women just take estrogen hormones to alleviate these issues? While estrogen supplementation, in the form of estradiol, can be beneficial for alleviation of some symptoms, it is not the hormone women need when they go through menopause. Research has found that hormone therapy in the form of an estrogen-progestin pill increases the risk of conditions such as heart disease, stroke, blood clots, and breast cancer.¹ It also can increase inflammatory markers, such as C-reactive protein, in the body.²

What are precursor hormones?

While estrogen and testosterone are important end products, there are more than just a couple of hormones that are affected by the changes that occur with menopause. In fact, there are several. Some of these hormones are called precursor hormones. Precursor means “a thing that comes before another.” When we’re talking about hormones, we mean precisely that — hormones that come before, or are converted into, other hormones. This supply of precursor hormones influences the supply or amount of other hormones.

Without precursors, we miss the benefits of the full hormonal cascade working together for the benefit of the body as a whole. Each precursor plays a role in our health and well-being. If we miss the precursor, we can miss its benefits. This does not mean there is no benefit to taking hormones like estrogen or testosterone. There are times when taking estrogen or testosterone is needed because a patient cannot convert well even with all the right amounts of precursors. But the amount of estrogen or testosterone will be less because the entire hormonal cascade is being fed. If you go straight to hormones like estrogen and testosterone and do not include a well-rounded hormonal program, you will lose the many benefits of the other hormones. Each hormone, whether considered a precursor or not, has specific benefits to the body.

Pituitary and adrenal gland hormones

Our bodies rely on endocrine glands to make hormones. The primary endocrine glands are the pituitary, pineal, thymus, thyroid, and adrenal glands, as well as the pancreas. Many of the precursor hormones come from the pituitary or adrenal glands. Adrenal glands are located above the kidneys, and they produce important hormones such as sex hormones and cortisol. They produce these hormones in response to signals from the pituitary gland, located in the brain. The pituitary gland responds in turn to signaling from the hypothalamus, also located in the brain. While this is not an exhaustive list, we want to share some important hormones produced by the pituitary and adrenal glands.

Two hormones produced by the pituitary gland (specifically, the anterior pituitary) are follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Additionally, though the posterior pituitary gland doesn’t produce hormones on its own, it plays an important role in storing and secreting hormones produced by the hypothalamus, including oxytocin and antidiuretic hormone (ADH).

Specific hormones produced by the adrenal glands include estrogens, cortisol, androstenedione, testosterone, pregnenolone, DHEA, and progesterone.

How hormones change during menopause

We want to review a few key hormones that go through significant changes — their functions, how their levels change during and after menopause, and what this means for the body’s function.

FSH and LH

Follicle-stimulating hormone (FSH) is made by your pituitary gland and is important for sexual development and functioning. FSH controls the menstrual cycle and stimulates the growth of eggs in the ovaries. After menopause, this hormone tends to increase.³ FSH causes ovarian follicles to enlarge and produce estrogen. Over time, in menopause, these follicles become fewer, causing decreased levels of estrogen as women age. Because of this lack of estrogen production, FSH increases to try to produce more. With no estrogen feedback to turn off FSH production, it stays continuously elevated after menopause. Raised FSH and lower estrogen may cause the characteristic hot flashes of menopause.⁴

Luteinizing hormone (LH) is produced and released by the anterior pituitary gland and also works to control the menstrual cycle by aiding in ovulation. LH levels rise right before ovulation.⁵ Too little or too much LH can create problems with infertility and reproductive complications.⁶ During menopause, the reduction in estrogen causes elevated LH levels.⁷

Estrogens

The main source of estrogen comes from the ovaries, but adrenal glands and fat tissues can also make smaller amounts. Estrogen is composed of estrone, estradiol, and estriol — the latter two are more important in hormone therapy. With decreases in estradiol and estriol, women may experience symptoms such as more frequent UTIs, vaginal pain, joint pain, headaches, memory loss, and mood changes, to name a few.

• Estrone comes from the ovaries, fat tissues, and adrenal glands. It is a weaker estrogen and tends to go up with the increased belly fat typical of menopause. Estrone can be inflammatory, and an increase in levels is not ideal.
• Estradiol plays a large role in puberty and reproduction and is the most powerful of the estrogens. It also plays an important role in bone health, cholesterol control, brain health, heart health, and skin health, as well as the health of other tissues.
• Estriol is the weakest form of estrogen. It typically increases during pregnancy, though it is present throughout a woman’s lifetime. It decreases after menopause, and because it is weaker, it can be helpful in hormone therapy — it may alleviate some menopausal symptoms while also not increasing the risk of breast cancer.⁸

Cortisol, androstenedione, and testosterone

Cortisol — With all the changes that occur in the body, it’s not abnormal for cortisol levels to rise, as cortisol is commonly known as the “stress hormone.” However, if the adrenals focus on producing cortisol, they may not be able to produce the amount of hormone precursors needed for optimal function.⁹

Androstenedione is an important hormone in the production of testosterone and estrogen. The adrenal gland makes most of it, with only small amounts secreted by the ovary. After menopause, women produce nearly half the amount of this hormone as before, which can have implications on the production of testosterone — needed for mood, skin, bone, and cognitive health.¹⁰

Testosterone — As a normal process of aging, there is a reduction in testosterone in females, seen more specifically in women going through menopause. The ovaries play a significant role in producing testosterone, but during menopause the hormones produced by the ovaries decrease, causing lower testosterone. Testosterone can also be produced in the adrenal glands.¹¹ Lower levels can affect energy, mood, sex drive, and cognitive function. Testosterone is very important for women — it helps with bone, skin, and nail health, and has possible neuroprotective properties.¹²

Pregnenolone, DHEA, and progesterone

Pregnenolone is produced by the adrenal glands, made from cholesterol in the body, and produced in the brain, where it’s considered a neurosteroid. It is a precursor to progesterone as well as DHEA; DHEA then converts to androstenedione, which converts to testosterone and estrogen.¹³ Because its role as a hormone precursor is so important, it is often referred to as the “grandparent precursor.”¹⁴ Pregnenolone has many important neurological functions, including neuroprotection, neuroplasticity, neurogenesis, and regulating mood and memory,¹⁵ as well as assisting with weight loss, libido, and overall energy. Like many other hormones, it decreases with age. Low levels have been associated with depression, fatigue, low libido, loss of bone density, and loss of muscle mass. There is promising research on the effects of pregnenolone therapy on conditions such as schizophrenia,¹⁶ depression,¹⁷ and memory loss.¹⁸

Dehydroepiandrosterone (DHEA) is an extremely important precursor hormone, synthesized from cholesterol through pregnenolone by the adrenal glands, and able to convert into other hormones like testosterone and estrogen. Levels are typically highest when we are young adults and gradually decrease as we age — potentially as much as 80% below our highest levels.¹⁹ Low DHEA is associated with low libido, reduced bone mineral density, heart disease, and osteoporosis in women. Sufficient levels are associated with brain health,²⁰ immune function,²¹ energy, bone metabolism,²² blood sugar regulation,²³ and healthy libido.²⁴

Progesterone plays a large role in menstrual cycles and in signaling the uterus to thicken in the event of pregnancy. During and after menopause, progesterone levels decrease significantly. Progesterone is also able to counter the effects of cortisol before menopause; afterward, this cushion weakens. Under high stress, the body also produces cortisol over progesterone, which can cause insomnia, low energy, digestion problems, weight gain, low sex drive, and more.²⁵ Clinically, we have seen supplementation with progesterone help restore restful sleep in individuals with low progesterone, enhance energy, and increase sex drive (since it does convert into testosterone). Progesterone also helps block aldosterone receptors, which can promote water retention and swelling.

What does bioidentical, functional HRT look like?

When the ovaries shut down, they no longer produce estrogen and progesterone. This means the adrenals have the heavy burden of taking over much of the hormonal work. Therefore, it’s important to support the adrenals before, during, and after menopause. The hormones we use are bioidentical — structurally identical to the hormones your body makes — a meaningful distinction from the synthetic progestin used in the older research that gave HRT its reputation.

Importantly, if there is a thyroid issue that has not been addressed, the body will depend more on the adrenals as well. If the body is already relying on the adrenals and then menopause occurs, women can run into a lot of issues. (This reinforces the need to check the thyroid and support it, if needed.) The thyroid gland has a strong influence over all the hormones — and more — that we’ve talked about. See menopause and the thyroid for how these two intertwine.

As discussed, it may not be ideal to just directly take testosterone or estrogen, as there are risks associated with taking only these hormones, and you can also miss out on the benefits of the precursor hormones. At our office, we approach HRT with a holistic and functional medicine-based perspective. It is very important to us to look at the whole picture of the hormone cascade in order to provide the right hormonal support.

Midlife is a transition to move through with real support — not something to simply endure until it passes.

Hormones we may use to support women during menopause

• Pregnenolone — the “grandparent” precursor. Once synthesized, it can convert to DHEA or progesterone; DHEA can then be precursor to androgens and estrogens, and progesterone can lead to cortisol, aldosterone, androstenedione, estrogen, and testosterone. It’s also important for the health of the liver, pancreas, pituitary gland, skin, and reproductive tissues, and for neurological health.²⁶ A wonderful hormone to support the endocrine system after menopause, under the guidance of a skilled practitioner.
• DHEA — synthesized from cholesterol through pregnenolone by the adrenals. It can counter potentially problematic hormones such as cortisol and is a precursor to specific estrogens and testosterone. DHEA helps with brain health, memory, immune function, blood sugar regulation, energy, and bone metabolism.²⁶
• Progesterone — helpful to ease anxiety and provide calm. Classified as a neurosteroid, it helps the nervous system function properly²⁷ and is a great choice at night for women having trouble sleeping. Note this is the bioidentical form of progesterone; progestin is the synthetic form and may not work the same. In the research on HRT risks noted earlier, participants were given estrogen combined with progestin, not progesterone.²⁸
• Estradiol — the strongest of the estrogens, able to help with a myriad of issues. We use products that couple the estrogen with progesterone (not progestin). When estrogen is not balanced with progesterone, it can stimulate growth of the uterine lining, which can increase the risk of endometrial cancer.²⁸
• Testosterone — we often see that DHEA feeds into testosterone, but there are times when it does not. In that case, we make sure precursor hormones are adequate and refer out for testosterone replacement.

Testing and dosing

How do I know if I need HRT?

We recommend that women start getting hormone panels done yearly starting anywhere from 35–40 years old. This is often the time a hormonal decline can start and symptoms can creep in. Women should have a hormone panel run when they start to notice menopausal symptoms or are postmenopausal. Each hormone is influenced by another, so it’s important to run a full hormone panel.

How do you know if you’re adequately dosed?

We will typically give a small starting dose and then build on that based on patient response and follow-up hormone panels. Hormone panels can be done every 6–8 weeks, after the hormone has had time to build up in the blood and adequate levels are maintained. Maintenance panels can be done every six months to a year to ensure hormone levels continue to be appropriate.

What if I’m taking hormones but was never retested after starting?

Each time a new dose is given, it should be retested in 6–8 weeks to assess whether the dose is enough or too much. We have often seen women come into the office on estrogen or another hormone whose blood levels are far above lab range for HRT. This can be dangerous — as mentioned, high estrogen can drive cancers. Proper clinical care includes retesting to ensure levels are not too high or too low. We also think this is where a lot of the concerns come from with HRT: unfortunately, HRT has developed a bad reputation because of inadequate follow-up testing. This misinformation has caused many women to miss out on HRT’s benefits.

We have seen the benefits of functional medicine-based HRT in our patients, and we are excited to support you in this journey to health. Please contact us if you have questions.