October 16, 2003, Forum Presentation

Menopause: When is Hormone Therapy Appropriate?

Dr. Vicki Holmes and Sarah Nixon-Jackle

Tonight, we'd like to take a different approach to discussing options for women needing help with menopause. We are going to present three case studies and explore the various options. This can be a complicated task as we will see!

Case 1 | Case 2 | Case 3

Case 1: Mrs. O.

This 54 year old woman is experiencing hot flashes several times in a day—she gets looks from people at work every time she asks, "Is it hot in here or is it just me?" Of course, she has tried the usual—wearing layered clothing so she can takes things off when she overheats. She wears cotton tops, sleeveless preferred. She's still menstruating but less often and the flow is unpredictable. She sees her doctor who gives her half dose of the topical preparation, Estrogel. She's told that when her periods stops. she needs to return and get started on progesterone.

All is well for six months, but then the night sweats start. She's missing sleep and starts complaining about her husband's snoring and the neighbours' dog barking. Her last period was four months ago. She's also getting very irritable. She has lots of stress with uncertainty at work, and her husband is ill.

She's obviously suffering from symptoms of menopause. Some other symptoms may be headaches, sudden symptoms of abdominal bloating, redistribution of body fat, the development of new allergies, palpitations, vaginal dryness leading to painful intercourse, even rogue hairs—those long chin hairs that seem to develop overnight!

Before making a decision about hormone therapy (HT), there is more information you need about her family history, such as heart disease, thromboembolic disease, strokes, breast cancer, Alzheimer's disease. You need to know more about her personal history as well.

Her mother died of cancer of the pancreas at 78, her father, of stroke at 86. She has several siblings—their only significant illnesses are hypothyroidism, hypertension, and osteoporosis. Osteoporosis is very prevalent on her mother's side. with her grandmother and two aunts having had fractured hips. Her maternal aunt had cancer of the colon. Her paternal grandmother had significant depression at the time of menopause— "involutional melancholia" they called it in those days. There is Alzheimer's Disease (AD) on her father's side.

Personally, she fractured her ankle 7 years ago and was found to have osteopenia at age 47. Other than hypothyroidism, she's in excellent health.

There's no question that the symptoms she's experiencing are related to menopause and she would greatly benefit from HRT. There are no contraindications to her using them, and along with symptom control, there may be other benefits as well. With HT, there's a 34% reduction in bowel cancer and 35% reduction in osteoporosis. The question still exists whether Alzheimer's Disease AD) is helped or hindered by HT.

(The Women's Health Initiative (WHI) study looked at 4,532 women 65 and older who were on Premarin 0.625 and Provera 2.5 mg per day for an average of 4.05 years. An equivalent of 22/10,000 on placebo vs. 45/10,000 on the medication developed AD. They wonder if it was due to tiny strokes, which looks a lot like AD. This is contrary to a review of 14 epidemiological studies that showed a 46% reduction in HT users. The Cash County Study showed that women who used HT had a 41% reduction in AD compared to the non-user women and a 33% reduction compared to men. This was seen if women had used HT at an earlier date, or, if current users had been on at least 10 years. Maybe we should go on NSAIDS (Advil, Motrin, or many other arthritic medications), since they reduce the incidence by 28%.)

For bowel cancer prevention, most people know you should reduce the red meat in your diet as well as processed meats, sweats and desserts, fried food and increase fibre in the form of fruits and vegetables. Bowel cancer is higher in smokers and men who drink more than 2 drinks of alcohol per day and women who drink more than one alcoholic drink per day, as well as people with a sedentary lifestyle. Bowel cancer is reduced by taking folic acid and calcium. By having a yearly test of your BM for occult blood, the mortality can be reduced by 15% by picking up on the cancer early.

What HT would be recommended?

It seems that after the WHI, many switched to prometrium, the progesterone that is bioidentical to what we have in our bodies. A recent article showing that trans-dermal HT (ie patches or cream) had fewer incidences of thromboembolic events (stroke or deep venous thrombosis, pulmonary embolus) than oral estrogen. It is bioidentical to your own estrogen as well. Since she is so close to having her periods stop, she may want to use the progesterone cyclically for a few months to avoid unexpected bleeding. This is taken for 14 days/month or every other month to minimize the length of time on progesterone. Prometrium has a lovely side effect—it promotes better sleep. The length of time on HT would likely be 3-5 years, reviewed as new evidence becomes available.

Case 2: Mrs. T

Mrs. T. is 47 years old. She had breast cancer last year and has completed chemotherapy and radiation. Initially she was OK, but for the last 5 months, her periods have become erratic and she is finding that dealing with her cancer is overwhelming. She's getting night sweats, not sleeping well, and her mood changes are dramatic. Her disfigurement from the surgery is causing difficulties in her relationship with her husband, mostly on her part, and her 18 year old daughter is seeing someone she doesn't approve of. She's been told that HT is not an option and she's desperate to find a solution.

This is a big issue. Her quality of life is threatened. Two important studies have come out this year—the WHI and Million Women Study. The Million Women Study is an observational study of 1,084,110 women 50 to 64 years of age between 1996 and 2001. Current users had a 30% increase in developing cancer, those on progesterone as well as estrogen had a higher rate. This rate decreased to the expected rate after 5 years of discontinuing the drug. There was no difference in mortality between the two groups. In the WHI, the women were older—66% were over 60 when they started. There was a 26% increase in the rate of cancer after three years, lower in the first two years and crossing over in the fourth year. 25.9% vs 15% had regional spread. The problem with the study is that they were older woman who therefore had a higher incidence based on age anyway and 25% of them had been on HT prior to going into the study. The increase in actual numbers was from 30/10,000 women in the control group to 38/10,000 in the women on HRT. These are relatively few in number but there is an increase.

In the journal Menopause, vol 10, no 4, 2003, an interesting article appeared by Decker, Pettinga et al. They looked at breast cancer survivors, 277 of whom chose to go on HT, carefully compared to matched controls. The mean time from cancer to estrogen replacement therapy (ERT) was 3.61 years, with the median being 1.88 years. They were on it for an average of 3.7 years. 92% found relief from hot flashes, 89% from vaginal dryness and painful intercourse, and 88% from reactive depression and mood changes. They were followed from 1984 to 2000. They had had either ductal CIS (carcinoma in situ i.e. non-invasive cancer of the duct) or infiltrating breast cancer. There was no evidence of increase in recurrence of their cancer or metastases. There was an improved survivor rate, with 6% death in controls and 3% on ERT.

Mrs. T needs help from a team approach. Two of the drugs we use in cancer patients may be of great benefit to her. Anti-depressants Effexor and Paxil have shown about a 60% reduction in hot flashes and have some benefit on sleep. It may help her to cope with some of her other issues as well. Gabapentin is an anticonvulsant that may be of help in reducing hot flashes. The dose ranges from 300 to 2400 mg /day.

Many women benefit from discussing their problems with other women. The HOPE group in town does a wonderful job of group activities, retreats and are a good source of information. We anticipate eventually getting groups together through the Menopause Centre.

As for her insomnia, good "sleep hygiene", a ceiling fan to cool one off, wearing ear plugs to keep out noise, avoiding caffeine and alcohol as well as medication may be of some help.

Case 3: Mrs. TH.

Mrs. TH. is 69 years old. She'd been on HT for 10 years but got frightened by the WHI report last summer and abruptly quit taking her meds. She's had a difficult year—initially the hot flushes were unbearable but she got through that and they aren't intolerable now. She does have insomnia and wonders if she can get some help with that. Since stopping her hormones, she's been complaining of vaginal dryness, pain with intercourse, loss of libido, urinary frequency. She smokes 1/2 packages of cigarettes a day.

Investigations show that her total cholesterol is elevated to 6.5, her LDL is 5. Her mammogram is normal. Her bone density has worsened over the last two years and is now 2.4 SD below young females at the hip, and 2.6 below at the lumber spine.

Family History: Her father died suddenly of a heart attack at 50, mother had a stroke at 65, her 62 year old brother had a quadruple bypass. They all smoked. Her aunt had breast cancer at 65, and died recently at 80. What should she do?

There are several things she must do:

STOP SMOKING! That is the single most important thing that can increase her longevity.
She needs to exercise. It is a little late in the game—if she were 50 and did 7 hours a week of moderate to strenuous exercise a week, she could reduce her breast cancer risk by 21%. To treat her osteoporosis she needs a combination of weight bearing exercises like walking, and weight and balance training. Certainly her risk of developing heart disease will be reduced. A recent study even showed that immunity is improved by exercising! (It also increases your androgens and has a positive effect on your libido!)
She has osteoporosis and needs to be treated. Adequate calcium is necessary (14 to 1500 mg of calcium/day) as well as 800iu of vitamin D. Raloxifen (Evista) is also a possibility—it's an estrogen receptor modulator that prevents vertebral fracture and has a positive effect on cholesterol (40% fewer cardiac events in high-risk women as well as a 6% reduction in strokes). There was a 72% reduction in the new diagnosis of breast cancer found in a large study. There may be a slight increased incidence of hot flushes, but not usually enough for women to withdraw from the drug. Bisphosphonates (Didrocal, Fosamax and Actonel) are also very effective medications for reducing the fracture rates in osteoporotic women.
Heart disease. She has a poor family history of heart disease, she is a smoker and has elevated cholesterol. She needs to be on a low cholesterol diet, stop smoking, get active and go on a 'statin'. These drugs act on the liver to reduce cholesterol, have a favorable outcome on heart disease, stroke and may have some benefit on osteoporosis.
She has signs of urogenital aging. The vagina, vulva, urethra and bladder are very dependent on estrogen. Signs of vaginal atrophy are dryness, frequent infections, pain with intercourse, reduced arousal and less intense orgasms. Signs of urinary aging are frequent voiding, getting up to void at night, pain on voiding, and frequent urinary infections. Vaginal preparations may be very helpful:
1. Lubricants: KY, Astroglide, "Oh My"
2. Replens: to restore vaginal mucous production
3. Local estrogen: Premarin, Vagifem (tablet), and Estring (plastic ring placed in the vagina).
These last two are not absorbed systemically and can be safely used in women for whom oral estrogen is contraindicated. They can bring about significant improvement. She might also consider using oral or topical testosterone. This can improve arousal, intensity of orgasm, and may be beneficial in osteoporosis.

Conclusion: As you can see, there are many things to consider. These three cases are typical of those I see every day. Every woman is unique in terms of her own history, family history and preferences. There is no 'magic bullet' for everyone and treatment must be individualized.