"Refreshing" menopause: from frozen ovaries to hormone therapy
Issued in the 950th issue of China News Weekly, 2020.6.08
Outsiders generally can't guess Zou Yi's age. Just looking at her appearance, there were no obvious wrinkles in her eyes and neck. Under a white slim sportswear, there were exquisite curves, and there was no trace of fat on her waist and back.
No insomnia, no anxiety, no muscle aches... An 8-page health questionnaire, Zou Yi answered it in three or two minutes, and there were no adverse symptoms. Unlike nearly 90% of patients of childbearing age in the waiting area of the Department of Endocrinology of Beijing Obstetrics and Gynecology Hospital, Zou Yi came to see the menopause clinic. At the end of the questionnaire, the doctor routinely asked a privacy question: "How is the life of the couple?" "At least once every two weeks." Zou Yi answered.
"Can you see me in my sixties?" Zou Yi said down the stairs. Twenty years ago, she first visited the menopause clinic because of paroxysmal fever and sweating. Since then, she has received menopausal hormone replacement therapy (MHT) and has a physical examination once a year. Since then, except for the symptoms that appeared in her early years, she has hardly experienced torture in menopause, and her osteoporosis has not been committed for more than two decades.
"It's not that I don't pay attention, but I don't know. Many female patients actually don't know that symptoms such as insomnia, muscle soreness, and foreign body sensation in the throat are caused by the decline of estrogen in menopause, and they don't know where these diseases can be treated and where to go." Capital Medical Ruan Xiangyan, director of the Endocrine Diagnosis and Treatment Center of the Beijing Obstetrics and Gynecology Hospital affiliated with the University, told China News Weekly that it is estimated that there are currently more than 200 million menopausal women in China, and over 80% are plagued by menopausal syndrome, but the actual consultation rate is only about 3%.
Before finding the menopause clinic, Wang Yali had seen neurology and traditional Chinese medicine more than ten times. From the age of 49 to the present, she has been menopausal for ten years, insomnia for ten years, and has a headache at night, but she can’t fall asleep, like turning on a night light and falling asleep. Down to earth. But she never linked insomnia to menopause.
In 2015, the National Center for Health in the United States surveyed 2,800 perimenopausal women aged 40 to 59 years. During perimenopause, the female ovarian function began to decline to the period of 1 year after menopause. More than 25% of the respondents had sleep disorders. At least 4 nights a week, it is difficult to fall asleep or easy to wake up in the middle of the night, more than 30% sleep less than 7 hours a day. Studies have shown that changes in hormone levels can affect sleep duration and quality.
As the most important gonadal organ, a woman’s ovaries bear both physiological functions of making eggs and synthesizing estrogen. The number of follicles in the ovary is fixed. After entering puberty, women generally discharge a mature follicle every month. In order to be fertilized, the rest of the same group of accompanying follicles automatically apoptosis. At this time, the endometrium will also thicken under the action of estrogen, ready to receive sperm eggs, if there is no fertilized egg implantation within two weeks, the endometrium will fall off due to the decrease in the concentration of estrogen and progesterone, which is menstruation Coming.
With the increase of age, the follicles continue to decrease and become exhausted. The functions of ovulation, menstruation, and conception cease. The estrogen responsible for regulating reproduction continues to decrease. At the same time, the level of pituitary gonadotropin increases, which leads to the control of blood pressure, breathing, and heart beat. The autonomic nervous system breaks the original balance state, which leads to various discomforts. Insomnia is one of the manifestations.
"Some people have symptoms such as heart palpitations and heart tingling, but no evidence of organic heart disease can be seen in various examinations." Yu Qi, director of the Endocrinology and Reproduction Center of Peking Union Medical College Hospital and chairman of the Asia-Pacific Menopause Union, explained , "The arrival of menopause is an objective law, but women around the age of 50 are still the backbone of the family and work. They should care for themselves and care about their symptoms. They should see a doctor in time and solve them in a timely manner. "
When Wang Yali brushed his phone before going to bed, he accidentally saw the video of Yu Qi’s popular science lecture. It felt like he finally caught the life-saving straw. According to the treatment window period of “before 60 years old, within ten years of menopause”, Wang Yali had 4 months left. time. Early the next morning, she downloaded the hospital app, registered in the afternoon, and made an appointment to the clinic a week later. Check, evaluate, and decide on treatment plan. After two weeks of hormone replacement therapy, you can finally fall asleep naturally.
Yu Qi et al. conducted a survey of climacteric clinics or gynecological endocrinology clinics in 14 hospitals nationwide in 2008 for half a year. A total of 1,641 patients aged 40 to 60 completed questionnaires. The results showed that more than 70% of patients had symptoms of fatigue , 64.1% of patients have varying degrees of bone, joint and muscle pain.
"We also did a survey in Beijing. Muscle soreness is the first symptom of menopausal women." Yu Qi told "China News Weekly" that estrogen will promote calcium absorption and precipitation, estrogen decreases during menopause, and bone density Decreased, osteoporosis, weakened bone bearing capacity, resulting in muscle atrophy, resulting in symptoms of fatigue and soreness. The patient is not clear that this is a symptom of menopause, and most of them go to the hospital to register orthopedics.
Yu Qi had also consulted a patient with an uncomfortable throat. She had done laryngoscopes nine times in different hospitals, but no cause was found. Finally, she registered to the Department of Otolaryngology, Peking Union Medical College Hospital. The doctor saw her and recommended her to Gynecological endocrine, and finally relieved the symptoms through the combination of related hormones and antidepressant treatment.
Wang Yali's estrogen and progesterone supplement treatment has been carried out for two months. Another visible improvement is that the wrinkles have been "flattened". Before treatment, Wang Yali always feels dry skin, as if there are small insects crawling one by one, which is different from the dryness caused by skin dehydration during the season change. It cannot be improved by rubbing skin care products. The root cause is collagen after estrogen levels are reduced. Protein synthesis is reduced and the skin becomes thinner.
Before the new crown epidemic, Ruan Xiangyan would sit in the community hospital for half a day every week. Nearly half of them were menopausal patients. What surprised her most was that most women no longer have a husband and wife life after menopause at the age of 40 or 50, and even sleep in separate rooms. I don't know if it can be adjusted by treatment. Normal physical and psychological needs cannot be met, and some middle-aged families have conflicts.
Entering the menopause was regarded as an “older woman” in the past, and there would be no, no need or even a sex life. However, according to a survey by Pan Suiming, a professor of sociology at Renmin University of China, 53% of China’s 55-61-year-olds have a one-time monthly life. A study by American sex expert Kinsey pointed out that 94% of men and 84% of women still have sex after the age of 60.
"I often like to say that if a woman is a flower, the hormone is water." Ruan Xiangyan gave an example. The menopausal symptoms caused by the reduction of estrogen are not only hot flashes, sweating, and bad temper, but from head to toe, from the inside Outside influence. Various glands reduce secretion due to decreased estrogen levels, including saliva, tears, gastrointestinal digestive fluids, vaginal secretions, etc., the corresponding manifestations are dry mouth, dry eyes, indigestion, and some patients appear repeatedly Abdominal discomfort and hematuria. After gynecological examination, it was found that it was not due to infection, but due to decreased estrogen and thinned vaginal mucosa.
After symptoms of menopause appear, there are many ways to stay healthy. "Controlling diet, exercise, quitting smoking and drinking, and an enlightened attitude to life are fundamental, but the most effective drug treatment is related hormone replacement therapy." Yu Qi told China News Weekly.
The best "anti-aging artifact" is its own original ovaries. Profam, headquartered in the United Kingdom, has provided nine women under the age of 40 who wish to postpone menopause with the service of "freezing preservation of ovarian tissue" to remove part of the female ovaries and preserve them in a cold environment. After they enter the menopause, they transplant the ovarian tissue back into the body. The young ovaries are still the age at the time of transplantation. They continue to release estrogen and stay young. The company advertises that "delaying menopause for 20 years is not a dream." Between 7,000 pounds to 11,000 pounds, about 60,000 to 96,000 yuan.
The technology developed in the late 1990s was originally designed to help young women undergoing cancer treatment to protect their ovaries and preserve their ability to reproduce. Beijing Obstetrics and Gynecology Hospital is currently the only medical institution in China that has been certified to carry out clinical routine development of "ovarian tissue cryopreservation" technology. "In order to obtain cryoqualification, in addition to cryopreservation, there must be successful cases of transplantation. The more destruction," Ruan Xiangyan said.
Zhai Xin diagnosed myelodysplastic syndrome at Peking University People's Hospital in 2016. Chemotherapy should be performed before bone marrow transplantation. Ultra-large dose chemotherapy will cause permanent damage to the ovary. She was not married at the time and wanted to preserve her fertility. At the recommendation of the doctor in charge, she was sent to the Beijing Obstetrics and Gynecology Hospital through the green channel, and the ovaries on both sides were removed and frozen. After the operation, he returned to Peking University People's Hospital to continue cancer treatment.
"At present, as long as the relevant surgery is performed in Beijing, the patients, the attending doctors and the relevant hospitals have the awareness of ovarian function protection and need, we can cooperate to do it." Ruan Xiangyan said that the operation is not complicated, and part of the ovaries are removed under laparoscopy The skin is stored in a special transfer solution and sent to the ovarian tissue cryopreservation store for storage, and then moved back into the body when needed. Compared with frozen embryos and frozen eggs, which are also referred to as "assisted reproductive technology", the target of ovarian tissue freezing can be women of all ages, without having to wait until the childbearing age, the operation is simple, the damage is small, and the applicability is wide. A UAE Dubai girl suffering from congenital blood disease underwent ovarian tissue removal and freezing at the age of 9, transplanted back to the body at the age of 24, and gave birth to a healthy baby boy in London, England in 2016.
Ovarian tissue can be kept in the frozen storage for about 20 years, and the survival rate of transplanted back to the body is as high as 95%. If there are many frozen tissues, it can be moved back in batches. Generally, a few pieces of ovarian skin can be maintained for three to five years, etc. After ovulation, transplant a few more pieces. "The theory of postponing menopause for 20 years is theoretically feasible, but ovarian tissue freezing technology is currently only used for medical needs in China and has not yet opened up to social needs." Ruan Xiangyan said.
In September 2018, Zhai Xin moved back a few pieces of ovarian tissue after marriage, and the rest of the ovarian tissue pieces will be moved back one after another in the next ten years to extend the fertility period. After 3 months of menstrual cramps, the chloasma on Zhai Xin's face began to fade, and the menopausal symptoms such as sweating and irritability gradually disappeared. In recent months, she began to run to the gynecological endocrinology clinic, this time to prepare for pregnancy.
Will it cause cancer?
When Zou Yi initially received hormone replacement therapy, he also worried that the hormone would cause cancer, would he gain weight, would he have femoral head necrosis like SARS patients who received hormone therapy?
This hormone is not the other hormone. There are hundreds of hormones in the human body, which are produced by glands or organs. They travel through the blood and organ tissues like chemical messengers, transmitting specific signals. In the public impression, it is adrenocortical drugs that cause side effects such as weight gain and necrosis of the femoral head. Its functions include metabolizing sugars, proteins and fats in the human body, anti-inflammatory and anti-allergic.
"Just like exogenous supplementation after the failure of other organs, if the thyroid is not working, the thyroid hormone is supplemented, and the pancreas is not working. Inject insulin to prevent diabetes. After the ovarian function declines, in order to maintain the normal functioning of the body, supplement it artificially. Estrogen and progesterone are so simple." Yu Qi said.
Does estrogen cause cancer? The controversy has continued for decades, and the fate of estrogen supplement therapy has been twisted.
If you can travel back to any dynasty from the Sui and Tang Dynasties to the Ming and Qing Dynasties, or medieval Europe, there is a high probability that women will not experience menopause. At that time, the lifespan of women was about the same as that of ovaries, only about 40 years old. The earliest case of estrogen treatment for menopausal symptoms can be traced back to 1893. French scientist Bordeaux used injections of ovarian extracts to treat mental disorders in menopausal women. It was not until more than thirty years later that anatomists discovered that the real effect It is estrogen.
Pharmaceutical companies have also become interested in the production of estrogen. The cost of drugs from placenta extract to artificial synthesis has gradually decreased. In 1942, the U.S. Food and Drug Administration (FDA) approved "Bimex" for the treatment of flushing in women, which is a mixture of estrogen extracted from urine of pregnant horses. However, the use of Premarin was limited to menopausal women with severe symptoms such as hot flashes and night sweats.
What really makes estrogen supplementation a household name is a bestseller. In 1966, Robert Wilson, a obstetrician and gynecologist in Brooklyn, New York City, USA published "Permanence of Fangling", proposing that women's estrogen levels will decline after menopause, and their body shape and beauty will deteriorate. Menopausal women who do not receive hormone replacement therapy Will no longer be a real woman and declare that "menopause is completely preventable" "every woman can choose to remain feminine forever".
At the time of the second American women's liberation movement, Wilson declared that the book's view on menopause treatment was actually a way of women's liberation. The pharmaceutical factory took the advantage of advertising to find a young and energetic actress. No woman is not afraid of old age, estrogen has become a family health care medicine for many middle-aged and elderly women. By 1975, estrogen had become the fifth most commonly prescribed drug in the United States, with 26.7 million prescriptions, and the number of "Belly" drugs in the United States alone exceeded 5 million.
But voices of doubt and warning have always existed. In the mid-1970s, two authoritative studies suggested that estrogen is associated with endometrial cancer, which has completely stirred up the "estrogen-causing cancer" storm. By 1977, the FDA even ordered relevant pharmaceutical manufacturers to remind women on the patient's instructions that "the drug has a carcinogenic risk." In the same year, "Women and Sex Hormone Crisis" became the best-selling book leading the healthy life of a new generation of women with an overwhelming advantage. The book displays evidence of estrogen causing breast cancer, stroke, and thrombosis, and warns women not to overuse hormones to treat menopausal symptoms .
Soon, the medical community itself broke the "carcinogenic theory". New research shows that the increased risk of endometrial cancer is not due to the use of estrogen, but due to the decline in progesterone levels after ovarian function decline, and progesterone supplementation can also effectively prevent endometrial cancer. By the 1980s, the use of estrogen and progesterone had picked up again.
During the same period, a large number of observational and epidemiological studies have shown that the incidence of premenopausal women with coronary heart disease is only 1/10 to 3/10 of men, and with age, the incidence of coronary heart disease in women increases significantly, 55 to 70 years old Gradually reaching the peak, the incidence of coronary heart disease in bisexual patients tends to be consistent, suggesting that estrogen deficiency is related to cardiovascular disease, hormone replacement therapy may have a protective effect on the heart.
To verify this view, the National Institutes of Health launched a project called the American Women’s Health Initiative (WHI), which claims to be the largest randomized double-blind controlled prospective study in history. More than 16,000 postmenopausal women from 40 clinical centers participated in the trial. The research and follow-up for 13 years, but because of the unexpected discovery that the incidence of breast cancer increased by 26%, the project was finally completed in May 2002 The test was terminated on the 31st. The pros and cons of the menopause-related hormone supplement therapy caused by this research continue to this day.
"After more than ten years of research, it was found that the risk of breast cancer is progesterone, and estrogen alone reduces the risk of breast cancer. In the WHI study, menopausal women used an gestational hormone progesterone, which is now a synthetic progesterone. After the natural progesterone, the risk of breast cancer has dropped back to normal levels." Yu Qi said.
In 2017, the latest guideline of the American Menopause Society also adjusted the time limit for medication. Originally based on WHI research, it was recommended that hormones should not be used for more than 5 years, and the new version of the guideline was changed to "the idea that MHT treatment should stop after 15 years is wrong."
"This is equivalent to indirectly indicating that as long as there are no contraindications, it can be used all the time." Yu Qi explained. He also conducted research within Peking Union Medical College Hospital. Gynecological endocrinologists used menopause-related hormone supplementation for the highest proportion, followed by gynecology, and then other brother departments. The more they understand the pros and cons, the more they will choose to use it.
When will treatment begin?
Hormone supplement therapy has a consensus that within ten years after menopause and before the age of 60 is the treatment window period, the formation of this concept also stems from the above WHI research.
The results of the WHI trial at the time showed that "hormonal supplementation did not achieve the effect of preventing cardiovascular disease", contrary to the conclusions of a large number of observational studies. In this regard, gynecological endocrinology, epidemiology and pathological anatomy experts conducted a variety of stratified reanalysis, and found that the average age of the initial drug in the test population was 65 years and above, most of them already have a certain degree of cardiovascular Pathological changes do not support the purpose of "detecting preventive effects".
After the study population was regrouped by age and menopause years, the conclusions had new changes: women who started hormone replacement therapy within 10 years of menopause had a lower incidence of coronary heart disease than placebo groups, and began receiving hormones after menopause for more than 20 years The treatment is higher than the placebo group, that is, estrogen can only protect the cardiovascular system when it is supplemented early in menopause, thus forming the "estrogen application window period".
"For patients over 60 years of age, it is not recommended to start supplementing in principle, but if the patient's symptoms are very heavy and there are no obvious contraindications, it can still be analyzed and handled individually." Ruan Xiangyan gave an example, a 78-year-old patient found her Asked for hormone replacement therapy, and after the complete physical examination, there were no contraindications. I had received hormone replacement therapy before, and it really relieved her symptoms of hot flashes, sweating, insomnia, osteoporosis, and muscle aches. Ointment applied percutaneously.
In 1999, Ruan Xiangyan prepared the first menopause clinic in the country at Beijing Obstetrics and Gynecology Hospital. At that time, Ruan Xiangyan recalled that if people talk about "someone is menopause", it always has a slightly derogatory meaning, mostly referring to this person's grumpy and weird. In order to promote the new treatment concept, the hospital leaders invited the National and Beijing Women's Federation and the People's Congress to sit in the outpatient clinic. People can’t accept hormones for a while, so they will experience a full-body examination first. The whole set of imported medical examination systems include anti-cancer examination, mammary gland target, blood biochemical items, hormone level test, bone density test, nutrition assessment, etc. Contraindications, whether it can be treated with hormones, how to treat, and finally give personalized medication advice.
At that time, the menopausal medicine group of the Chinese Medical Association had not yet been established, and there was no written standard in China. Ruan Xiangyan took the young doctors of the department to translate English materials together, summing up experience while seeing a doctor. When meeting in the North Obstetrics and Gynecology Hospital, the newly-opened menopause clinic will always be promoted, and the hospital will be encouraged to experience it first, the acquaintance effect, and more and more menopausal patients come to the clinic.
"Nearly 1/8 of the outpatient clinics are menopausal patients, and the number is not large, but an obvious change is that now people who look at menopause, more than 90% will receive hormone replacement therapy." Ruan Xiangyan recalled this change It also happened in the last five or six years.
In 2019, the Department of Maternal and Child Health of the National Health and Health Commission released the "China Maternal and Child Health Care Development Report", encouraging women and children's health care institutions at all levels to set up menopausal clinics, promoting the construction of menopausal health specialists, and providing screening and evaluation of the health status of menopausal women. Nutrition, psychological, Sports counseling and other services to improve the quality of life of menopausal women. In 2018, the total number of menopause clinics nationwide reached 2.32 million.
Before the epidemic, Ruan Xiangyan's department could be described as "prosperous people". There were up to 20 doctors who came to study abroad in the same period. Almost all of them came with the task of "going back to build an outpatient department or department".
"It is a good thing to promote the menopause-related hormone supplement therapy, but because of the risks of hormone therapy, it should emphasize the standardization of treatment. Before taking the drug, you must go to a regular hospital for strict physical examination and screening. After treatment, you should regularly review and follow the doctor's advice "According to Ruan Xiangyan, since the establishment of the Pediatric Obstetrics and Gynecology Outpatient Clinic in North China, there has been no case of cancer caused by hormone therapy.
According to the "Chinese Menopause Management and Menopause Hormone Treatment Guidelines (2018)", there are 8 types of contraindications and 8 types of caution. Contraindications mainly include breast cancer, sex hormone-dependent tumors, and meningiomas. For patients with active venous or arterial thromboembolic diseases within the past six months, hormone therapy is not recommended. If you have uterine fibroids, endometriosis, epilepsy, asthma and other diseases, you must strictly follow the doctor's instructions and use hormone therapy with caution.
Different patients have different medication plans, and the specific medication type and method of administration vary from person to person. "However, after the hormonal drug Ke Lingmeng produced by Bayer was taken off the shelf, there were fewer drug options. Now there are only two or three drugs with a good plan." Ruan Xiangyan said that the treatment cost of MHT is not much, minus medical insurance. One hundred or two hundred yuan per patient per month is enough.
Menopause is a natural process in which women begin to age. In China, the average age of menopause is 49 years old. According to 2018 statistics, the average life expectancy of Chinese women can reach 82 to 84 years. "The advancement of medicine makes people's life longer, and how to make people live well is also the responsibility of medicine." Yu Qi said, "This is a process of constantly surpassing nature and returning to nature."
(In order to protect the privacy of patients, all the patients interviewed in this article are pseudonyms)
"China News Weekly" No. 20, 2020
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