A Metabolic Approach to Menopause:
Menopause is defined as the cessation of menstrual bleeding, and is said to have occurred when one year has passed from the time of the last period.
It represents the end of reproductive capacity and is caused by cessation of normal ovarian cyclical production of female hormones. It usually happens between the ages of 45-55, but is preceded by up to 10 years of hormonal fluctuations, (known as perimenopause), which can be associated with physical, psychological or cognitive symptoms of hormonal decline and accompanied by changes in the pattern of bleeding.
Menopausal symptoms are usually more severe when associated with a surgically-induced (ie removal of the ovaries), or chemically– induced menopause (the result of estrogen-blocking drugs such as Tamoxifen, employed in the treatment of breast cancer).
Menstrual bleeding can:
- Cease abruptly
- Occur at regular monthly intervals, but get progressively lighter
- Occur at shorter intervals i.e. every 2 ½- 3 weeks
- Occur at longer intervals and be associated with heavy bleeding or clotting
The last two patterns of bleeding can be explained and normalized by looking at the relative deficiencies and excesses of the main female hormones – Estrogen and Progesterone, as they are associated with a decline in the production of progesterone, in the presence of normal, low or high levels of estrogen.
Assessment of irregular, heavy menstrual bleeding can also involve ultrasound of the uterus and endometrial biopsy to rule out precancerous proliferation of the endometrial lining (endometrial hyperplasia)or uterine fibroids.
Hot flashes/insomnia/headaches; vaginal/bladder atrophy; mood/memory/cognitive concerns; changes in body composition/bones
Hot Flashes and night sweats per se are symptoms of vasomotor instability, and are a hypothalamic response to fluctuating hormone levels vs being diagnostic of estrogen deficiency. They may be exacerbated by stress hormones secreted by the adrenal glands. Sweating may also reflect excess thyroid hormone production.
Other symptoms may be more helpful in suggesting which hormones are likely deficient:
- Estrogen deficiency is associated with symptoms such as vaginal dryness, painful intercourse, and urine frequency, stress incontinence or cystitis, as part of the bladder (trigone) has estrogen receptors. It is also associated with *cognitive symptoms , such as short-term memory issues – eg forgetting where you left things, name & verbal recall; decreased ability to concentrate, reason, multitask and learn new things; and *emotional symptoms such as fatigue and depression.. *Estradiol modulates serotonin, noradrenalin and dopamine receptors and affects neurotransmitter production such as acetylcholine, GABA, and endorphins; also heightens sensitivity to nerve growth factor, which is responsible for growth of dendrites – the connections between nerve cells- in the brain.
- Other symptoms of Estrogen deficiency are osteoporosis (loss of bone density with increased risk of hip and vertebral fractures); with changes in blood lipids (lower HDL, higher LDL), decreased elasticity of small arterioles (elevated blood pressure), and increased platelet stickiness -culminating in an increased risk of cardiovascular disease; estrogen deficiency increases the risk of macular degeneration and cataracts; leads to thinning skin & wrinkles due to decreased collagen production and decreased moisture retention; and can be a factor in scalp hair loss and gum recession.
- Progesterone deficiency may be an issue long before menopause, where it is associated with problems such as fibrocystic breasts, uterine fibroids, premenstrual tension and headaches; the cause being anovulatory cycles or a deficient luteal (post ovulatory ) phase. In the perimenopausal years it is the first hormone to decline, and may lead to changes in the pattern of bleeding (either shorter or longer cycles, with heavier bleeding); insomnia, anxiety/irritability /depression and mood swings, joint and muscle aches and pains, fluid retention, hot flashes. In the early stages of menopause, hot flashes will often be relieved by supplementing with progesterone without additional estrogen. Progesterone deficiency has detrimental effects on bones, lipids & blood vessels.
- Estrogen/Progesterone balance (Estrogen Dominance, Functional Hypothyroidism, Insulin Resistance and Cardiovascular disease)
One of the parameters we look at in initial saliva tests is the progesterone: estradiol ratio…..
Normal or high levels of estrogen in the setting of reduced progesterone, is termed Estrogen dominance, and this will be associated with thickening of the lining of the uterus- endometrial hyperplasia- which is usually associated with pattern of skipped periods, followed by heavy bleeding and clotting. This can progress to endometrial cancer, so tests such as ultrasound of the uterus, and endometrial biopsy, are done, and the estrogen excess is balanced by progesterone supplementation. This can take the form of non-bioidentical progestagens in a pill or intrauterine form- but we prefer to use transdermal or oral bioidentical progesterone, for the reasons cited in the ESTER study.
Estrogen dominance is also manifested by breast tenderness and enlargement, abdominal, hip and thigh weight gain, and often symptoms of hypothyroidism – fatigue, fluid retention- in the setting of normal thyroid levels (functional hypothyroidism). It is associated with proliferation of breast tissue, and a heightened risk of breast cancer.
Additional symptoms may include agitation/panic attacks, poor sleep, headaches.
Factors that can promote estrogen dominance are
- obesity -fat cells contain an enzyme that converts adrenal hormones into estrogen
- and, of course, too high a dose of supplemental estrogen !!!
Progesterone excess usually only occurs with over-supplementation ie too high a dose; curiously enough this can cause desensitization of the progesterone receptors and symptoms of low progesterone!! ( but symptoms improve with reduction in dose).Too much progesterone in the setting of too little estrogen can result in abdominal weight gain, changes in blood lipids ; insulin resistance, depression, fatigue, myalgia, bloating and decreased libido.
Estrone (E1), Estradiol (E2), and Estriol (E3); Estrogen Metabolites
Estrone is produced in the adrenal glands, fat cells, and in the ovaries prior to menopause, where it is converted to estradiol. After menopause, when the ovaries cease to function, it continues to be produced in the adrenals and fat cells, and with declining levels of progesterone, it can be the dominant sex hormone. It has a proliferative effect on breast and uterine cells, and high levels are associated with an increased risk of breast and uterine cancer.
It is usually metabolized in the liver to 2-OH Estrone (a ”good” metabolite, which blocks stronger estrogen metabolites from binding to cells) and is excreted in the urine; there are 2 other enzymatic pathways: ie conversion to 16-OH Estrone (which binds to special estrogen receptors and has a strong stimulatory effect) and 4-OH Estrone (which can cause DNA mutations). Equine estrogens shift the metabolism towards 4-OH metabolites and also produce much more rapid mutagenic changes in cellular DNA
A low ratio of 2-OH Estrone : 16-OH Estrone is associated with breast cancer, and lower survival rates in those women who do have breast cancer (the ideal ratio is around 2)
This can be measured by a urine test,( recommended for women who are obese ie. who produce higher levels of Estrone, for anyone who has a family history of breast or uterine cancer, or who has themselves been previously diagnosed with breast cancer).
Certain foods, by virtue of containing a substance known as Indole-3-carbimole, can shift the metabolism of Estrone in favour of the good metabolite 2-OH Estrone; chiefly cruciferous vegetables such as broccoli, cauliflower, Brussels sprouts, cabbage, bok choy, kale, turnips , radishes… so, by changing your diet, or taking a supplement of 200-300mgs of I3C a day, you can offset the bad effects of too high levels of 16-OH Estrone.
Estradiol is the most potent estrogen and is produced in the ovaries premenopausaly from Estrone. It has beneficial effects on brain, bone, heart and circulation. It also improves mood, energy levels and sleep via its effects on serotonin and endorphin production. Many women will continue to produce this hormone in small amounts post menopause- however high levels are associated with an increased risk of breast and uterine cancer. Levels are drastically reduced by any surgical procedure which affects circulation to the ovaries such as tubal ligation or partial hysterectomy.
Estriol has a much weaker effect on breast and uterine cells; it does not promote breast cancer; in fact it may even have a protective effect, by blocking Estrone binding to receptor sites in breast tissue. and has been used in the treatment of patients who have had breast cancer. It is beneficial for vaginal and bladder symptoms; may help promote the growth of healthy bacterial flora in the bowel, and will help reduce hot flashes; but has no protective effect on bone, heart or brain.
By examining the benefits and side effects of the various estrogens and their metabolites, the preferred Metabolic approach to Menopause is to avoid oral estrogens, and estrone (E1), and use a combination of topical bioidentical E2 and E3 (BiEst) in combination with progesterone for balance. The ratio and dose of each will vary from woman to woman, based on symptoms and pre -treatment levels of the individual hormones. This is not a static approach, as a woman’s hormonal environment will change as she progresses further into menopause with declining levels of estrogen, and also of other hormones – such as thyroid hormones, the androgenic hormone, testosterone, and adrenal hormone, DHEA.
As discovered in the Women’s Health Initiative study, combined hormone replacement therapy (HRT) can be associated with a higher risk of heart disease, stroke and breast cancer- however this is not a blanket observation, and needs to be carefully qualified.
We know estrogen has beneficial effects on blood lipids, (it lowers “bad” LDL cholesterol, elevates “good” HDL cholesterol, lowers triglycerides), decreases arterial resistance, and a deficiency is associated with increased platelet stickiness… In fact, women generally do not generally exhibit an increased risk of heart disease and stroke (genetic factors and smoking aside) until after menopause. So why would estrogen replacement increase the risk of heart disease?
The answer lies in the ESTER study.. ie the heightened risk is associated with the use of ORAL Estrogen Replacement vs TRANSDERMAL estrogen (gel, cream or patch), and with certain kinds of ORAL PROGESTAGENS vs oral or transdermal progesterone. This is borne out with statistics on the heightened risk of thromboembolic disease associated with oral estrogens and certain classes of progestagens in birth control pills (OCPs).
The other side of the coin is that as one gets older, one’s risk of heart disease increases naturally; but the general consensus is that from the cardiovascular perspective, the benefits of HRT outweigh the risks for at least the first five years..
While prescribing transdermal HRT, it is always prudent to do a global risk analysis for cardiovascular and thromboembolic disease; ie search for risk factors such as undiagnosed or uncontrolled hypertension or diabetes mellitus; a family history of premature heart disease, thromboembolic disease and underlying clotting disorders: obesity (especially abdominal obesity; a waist circumference above 88cms for women is associated with increased risk of diabetes and heart disease); smoking; and to do a lipid profile. Some practitioners may also wish to evaluate CRP-hs, lipoprotein-A and homocysteine levels. (NB a history of previous VTE may not necessarily be an absolute contraindication for transdermal HRT eg transdermal progesterone)
Nutritional supplements may also help to lower the risk of cardiovascular disease- B6/12/ folate vitamins will help lower homocysteine; elevated CRP can be helped by taking fish oils, green tea extract and Co Enzyme Q-10. (Co Enzyme Q10 is lowered by statin drugs which are used for treating high lipids, so if you are on statins, supplementing with at least 100mgs Coenzyme Q10 a day is recommended)
Dietary measures such as a reduced animal protein (saturated fats), eliminate transfats (processed foods), high fibre diet, and regular exercise are also essential to reducing the risk of cardiovascular disease, and of course NO SMOKING!!!!
Risk of Breast Cancer
The major ongoing concern re HRT is centred around the increased rate of breast cancer as discovered in the Women’s Health Initiative study– which revealed a 22% increased risk, which translates into an extra 2 women with breast cancer per ten thousand on HRT.
Given that we know HRT improves the quality of life for women suffering menopausal symptoms, reduces hip fractures by 33%, reduces the incidence of colon cancer, improves cognition and lowers the risk of Alzheimer’s disease (by 40% in one study), and if given trans- dermally vs. orally, does not increase the risk of thromboembolic disease.. then we need to look at what general factors put women at higher risk of breast cancer, and what specific aspects of HRT increase this risk..
Genetics – testing for BCRA gene
A family history of premenopausal breast cancer, of breast cancer in more than 2 first degree relatives ( siblings, mother, daughters,maternal grandmother) may prompt genetic testing for the BCRA gene (associated with breast, uterine or ovarian cancer).
General risk factors
Early menarche/ late menopause/ no children; obesity-which is associated with higher total body levels of estrogen [ higher production of Estrone (E1) in fat cells, decreased sex hormone binding globulin, and therefore higher free levels of estrogen; and changes in estrogen metabolism]
These are chemicals which imitate the effects of estrogen, and are found in pesticides, plastics, cosmetics and synthetic hormones fed to animals. Prudent habits to follow would be to shop for organic foods, avoid processed foods, avoid plastic containers as much as possible- bottled water, canned food (tins are lined with—-); a good reason for not microwaving food in plastic wrap; avoid parabens in cosmetics etc
Certain post menopausal hormone patterns are associated with an elevated risk of breast cancer: estrogen dominance, insulin resistance, low melatonin , low levels of Vit. D; certain patterns of estrogen metabolism (see below)
Minimizing the risk of breast cancer while on HRT
The French E3N Cohort Study (Fournier et al published in Breast Cancer Res Treat Jan 2008)– looked at 80,000 menopausal women and followed them over 8 years
Conclusion – for women using Bioidentical Estrogen & progesterone- the risk of breast cancer was the same (RR1) to those never having used HRT !! In users of synthetic hormones the risk was increased by 70% Compared to women who had never taken hormonal replacement, the relative risk for those taking Estrogen alone-RR 1.29; Estrogen plus progesterone; RR1(see above) Estrogen plus progestagens RR1.69
- Using the lowest dose possible of estrogens;(transdermal vs oral dosing)
- Avoidance of equine estrogens: Equilin (present in Premarin) can take up to 13 weeks to eliminate from the body, as our enzymes are designed to break down human estrogen (eg estradiol) vs. horse estrogens.. That means synthetic equine estrogens can rapidly accumulate and stimulate the proliferation of breast tissue
- Balancing with progesterone (vs synthetic progestagens) to avoid estrogen dominance
- Cycle hormones so as to mimic natural premenopausal patterns- that is particularly important in the perimenopausal years; but a monthly break of 3-4 days is a good idea to prevent estrogen receptor tolerance .. this can be achieved by dosing for 26 straight days, and then take a break, or 6 days a week on, 1 day off, hormones
- Avoid Estrone (E1) and preferentially supplement with a mixture of E2 (Estradiol) and E3 (Estriol)
- Lose weight/reduce waist circumference so as to reduce the native production of Estrone
- Check for harmful estrogen metabolites in the urine ( the 2:16 OH Estrone ratio)
Although it is a male (androgenic) hormone, testosterone has many beneficial functions in women; it helps maintain muscle mass and tone (helps saggy skin), decreases body fat, helps maintain bone density, improves energy, drive, self -esteem and decisiveness, memory and libido ( sex drive).
It is balanced by estrogen, so when estrogen levels are low, or testosterone levels are high, symptoms such as oily skin, acne, facial hirsuitism and loss of scalp and pubic hair may appear.
Only a small portion of circulating testosterone is free, so measurement of blood total levels will not yield useful information.
Apart from declining levels due to menopause, low testosterone can be caused by adrenal fatigue, (chronic stress), birth control pills and cholesterol-lowering drugs.
High levels of testosterone (vs. normal levels with low estrogen) can be caused by adrenal disorders or polycystic ovarian syndrome (obesity, insulin resistance, infrequent periods, infertility, facial hirsuitism and acne).
Testosterone replacement may improve menopausal symptoms such as low libido, fatigue, anxiety; when given with estrogen it will also have beneficial effects on arterial resistance, lipids and vaginal dryness If given without optimizing estrogen levels, it may actually lower HDL (“good”) cholesterol, and increase plaque formation in the arteries , leading to increased risk of heart disease.
DHEA is an adrenal hormone, important for for energy, muscle mass, bone health, cell repair, immune function, and response to stress. It has beneficial effects on lipids; and is also thought to be important for libido. It declines naturally with age. Women can be very sensitive to supplementation, with excess doses showing up as acne, oily skin and hirsuitism. A declining ratio of cortisol to DHEA can be one of the earlier indicators of adrenal fatigue.
Bone composition is intricately related to hormonal balance; declining levels in midlife of estrogen (women) and testosterone (men) are associated with demineralisation of bone, leading to fragility and increased risk of fractures. Major areas affected are the vertebrae- resulting in loss of height, and compression fractures, which cause pain, wedging and forward curvature of the thoracic spine (Dowager’s hump), and the hip- resulting in hip fractures and loss of mobility.
Healthy bone formation is a product of a balance between the activity of osteoblasts ( bone-building cells) and osteoclasts ( cells responsible for the constant remodelling and repair of healthy bone), and the presence of adequate levels of trace minerals – Calcium, Magnesium, Boron, Manganese- and vitamins – esp Vitamins D and K.
Risk factors for osteoporosis:
- Menopause (bone is particularly dramatic in the first 2 years following menopause)
- Low testosterone (men), hyperthyroidism
- Prolonged episodes of amenorrhea (no periods)before menopause eg associated with Depo Provera treatments, anorexia nervosa, extreme athleticism
- Smoking, alcohol, excessive caffeine or soft drink intake
- Rheumatoid arthritis
- Medications such as anti-seizure meds, blood thinners, prolonged use of ant-acids or PPIs, Depo Provera injections, steroids
- Vit D deficiency
- Genetic factors
- Slim build
- Prolonged bed rest or immobility
Recommended intake of Calcium after menopause is now 1200mgs per day (includes all sources of calcium – dietary and supplements); too much Calcium has been associated with an increased risk of cardiovascular disease and kidney stones
Dietary sources of Calcium (other than dairy products):
Tofu, beans, nuts (almonds, walnuts, brazil nuts, pecans), greens, kelp, bony fish- (salmon, mackerel, sardines) etc.
Testing for Osteoporosis:
DEXA scan (bone densitometry); Ultrasound Sound heel bone; Urine testing for Dpd ( deoxypridinolone- a breakdown product of bone collagen- which is used as a biochemical marker of bone turnover- more useful for measuring response to HRT for osteoporosis).
FRAX scoring: this is a scoring system which is used to predict the 10year risk of developing a fracture if the DEXA scan reveals a low bone density
Vitamin D levels: 25-OH VitD3 levels are checked to ensure optimal dosing–because Vit D production is highly dependent on exposure to sunlight, we find a significant proportion of persons in northern latitudes are low in Vit D; this can have adverse consequences on the immune system as well as on bones; low levels of VitD are associated with higher incidences of various cancers, as well as lowered resistance to infections.
Treatment of Osteoporosis
As well as adequate intake of Calcium, Magnesium and Vit D, treatment of established osteoporosis may include any of the following categories of drugs
- Bisphosphonates (eg Fosamax)
- HRT – estrogen (females) or testosterone (men) replacement therapy
- SERMS (Selective Estrogen Receptor Modulators, eg Evista)
- Forteo (teriparatide- a recombinant form of parathyroid hormone)
- Prolia (Denosumab)
Commonly referred to as “middle-aged spread”, the characteristic weight gain seen in women in midlife is related to hormonal imbalances; whereas a relative excess of estrogen is associated with fat deposition around the hips ( and may lead to symptoms of hypothyroidism because of a blocking effect on thyroid hormone)- an excess of progesterone (from too high doses or progesterone without estrogen supplementation) will lead to an increased waist circumference ( and may predispose to insulin resistance).
Prolonged stress/chronic depression, is associated with elevated levels of cortisol, which leads to fat storage, muscle breakdown, and insulin resistance..
In turn, obesity increases Estrone production, increases the risk of breast and uterine cancer, and predisposes to metabolic syndrome- (hypertension, abnormal lipids, and insulin resistance- a precursor for heart disease and diabetes).
The solution is a combination of hormonal balancing, a low glycemic index , high fibre diet, and exercise (see section on Metabolic and Nutritional Medicine)
Sexual dysfunction is common in the menopausal years; a loss of interest in sex or libido , can be related to relationship problems, changes in body image and self esteem , chronic stress and depression, or declining hormones..
Chronic stress, as well as providing more immediate priorities, can shift the production of steroid hormones away from the sex hormones, as there are common precursor pathways. Often long-term relationships have settled into a dull routine that needs to be spiced up with a romantic interlude or a variation in normal sexual activity; if testosterone or DHEA is low, replacement can improve desire.
Painful intercourse is related to extreme estrogen depletion, resulting in thinning and drying of the vaginal wall, with eventual atrophy of tissue. Sometimes this is associated with bladder problems such as frequency, cystitis, or stress incontinence, or vaginal bleeding. An examination should be done to rule out infection, neoplasm (tumours) or prolapse.
Topical Estriol can be used; sometimes the addition of a small amount of testosterone can help, or BiEst ( a combination of Estradiol and Estriol). It should not be forgotten that estrogen replacement needs to be balanced with progesterone.. If there is diffuse perineal discomfort- vulvodynia- tricyclic antidepressants or anti-epileptic drugs(eg Lyrica) may be used in small doses for their modulating effect on pain. Urinary frequency/incontinence or interstitial cystitis can be addressed through oral medications, surgery, bladder instillations (DMSO) or intravesical Botox.
Anorgasmia may be caused by any of the above- relationship issues, stress/depression, medications (inc many antidepressants);hormonal deficiencies…some physicians use topical arginine to increase vaginal sensitivity; oxytocin (a pituitary hormone used in small doses) in sublingual or injection form have been used successfully, and if relationship issues are the problem , couples counselling with a therapist trained in sensate focus therapy may be of help.
As well as HRT (both conventional and bioidentical), approaches to menopause have included
- Non- hormonal Pharmacotherapy: Clonidine (Dixarit), Effexor (antidepressant)- helpful for hot flashes and night sweats
- SERMS – eg Raloxifene (Evista); selective estrogen receptor modulators do not have a stimulatory effect on breast tissue ( ie no increased risk of breast cancer) and are helpful for hot flashes; they have a mild positive effect on blood lipids ( lower total and LDL – “bad” cholesterol); but are less effective than estrogen for improving bone density, lowering triglycerides and elevating HDL “good cholesterol”, and have no effect on estrogen receptors in the brain:
- Herbal medications- Black Cohash, Chasteberry, and phytoestrogens such as Red Clover, have been demonstrated in some studies to have beneficial effects on hot flashes and night sweats, but have no effects on cardiovascular system, bones or cognitive function
- Chinese medicine- some practitioners use a combination of acupuncture and Chinese herbs such as Dong Quai , to relieve vasomotor symptoms
Chasteberry lowers LH and prolactin secretion, elevates progesterone and has a diuretic effect: Black Cohash is said to have an estrogen balancing effect: Dong Quai and Red- leafed Clover are phytoestrogens ie have estrogen-like effects.
Menopause, and the years leading up to it, is often a time of existential crisis for women living in Western societies; in a youth-orientated image-conscious social milieu, women may find themselves adjusting to changes in their physical appearance, and loss of reproductive function against a background of relationship issues – separation, divorce, widowhood; perhaps not having found a partner to father their children. Re-entering the dating scene at fifty, encountering declining libido or other sexual dysfunction while in a long term relationship -may also be stress provoking. On the other side of the coin, coming to terms with the empty nest syndrome, and becoming caregivers for elderly parents, may be the straw that broke the proverbial camel’s back..
In the working environment, they may find declining memory and energy levels a challenge, when competing with women twenty years their junior; or find hormonally mediated mood disorders or hot flashes an impediment to their productivity.
Facing these midlife challenges can provide an opportunity for personal growth and development- a chance to re-evaluate one’s priorities and perhaps set out upon a completely new path with yet- to- be- discovered horizons.
At The Lazer Room, we offer one-on-one counselling, group sessions, and seminars in Stress Management, Relaxation Training, and Self- Actualization- see relevant section on website.