Hormone replacement therapy side effects infographic #HRT

The Effects of Hormone Replacement Therapy on the Body.

Hormone replacement therapy can relieve unpleasant symptoms of menopause, but there are some side effects and health risks that should be considered.
Sources and more information

Heightened fracture risk for some antidepressant drug used to reduce symptoms of the menopause

Menopausal women using SSRIs “at risk for fractures”

image of crutches
SSRIs – a class of antidepressant drug used to reduce symptoms of the menopause – may increase the risk of bone fractures, according to new research. Image of Crutches by mnd.ctrl.

2015 Study Abstract

Selective serotonin reuptake inhibitors (SSRIs) were recently approved by the FDA to treat vasomotor symptoms associated with menopause. No prior study has directly examined whether fracture risk is increased among perimenopausal women who initiate SSRIs or among a population of women without mental disorders more generally.

Female patients without mental illness, aged 40–64 years, who initiated SSRIs were compared with a cohort who initiated H2 antagonists (H2As) or proton-pump inhibitors (PPIs) in 1998–2010, using data from a claims database. Standardised mortality ratio weighting was applied using the propensity score odds of treatment to adapt the distribution of characteristics among patients starting H2A/PPIs to the distribution among SSRI initiators. Poisson regression estimated risk differences and Cox proportional hazards regression the RR of fractures among new users of SSRIs versus H2A/PPIs. Primary analyses allowed for a 6-month lag period (ie, exposure begins 6 months after initiation) to account for a hypothesised delay in the onset of any clinically meaningful effect of SSRIs on bone mineral density.

Fracture rates were higher among the 137 031 SSRI initiators compared with the 236 294 H2A/PPI initiators, with HRs (SSRI vs H2A/PPI) over 1, 2 and 5 years of 1.76 (95% CI 1.33 to 2.32), 1.73 (95% CI 1.33 to 2.24) and 1.67 (95% CI 1.30 to 2.14), respectively.

SSRIs appear to increase fracture risk among middle-aged women without psychiatric disorders, an effect sustained over time, suggesting that shorter duration of treatment may decrease fracture risk. Future efforts should examine whether this association pertains at lower doses.

Sources and more information

Menopause Transition: most Women experience Hot Flashes, Night Sweats for over 7 Years

Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition

menopause Hot Flashes image
Research suggests that those with early and frequent menopause symptoms can expect them to last seven years

The menopause is part of the natural ageing process and is caused by a change in the balance of the body’s sex hormones.
Frequent menopausal vasomotor symptoms (VMS), including hot flashes and night sweats, lasted for more than seven years during the transition to menopause for more than half of the women in a large study and African-American women reported the longest total VMS duration, according to a new article published online by JAMA Internal Medicine.

Women who experienced hot flashes and night sweats at a younger age tended to have them last longer, the study found, as did women with less education and greater levels of stress.

Sources and more information

  • Hot Flashes, Night Sweats Last for 7+ Years in Many Midlife Women, JAMA Internal Medicine Releases for February 16, 2015.
  • Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition, doi:10.1001/jamainternmed.2014.8063, articleid=2110996, JAMA Intern Med. Published online February 16, 2015.
  • Vasomotor Symptom Duration in Midlife Women—Research Overturns Dogma, doi:10.1001/jamainternmed.2014.8099, articleid=2110993, JAMA Intern Med. Published online February 16, 2015.

HRT: short-term use of hormone replacement therapy linked to ovarian cancer risk increase

HRT increases ovarian cancer risk

HRT menopause treatment ‘doubles the risk of getting ovarian cancer’

HRT at menopause image
Women who undergo hormone replacement therapy (HRT) have a ‘significantly increased’ risk of developing ovarian cancer, according to a major new study.

Researchers from the University of Oxford analysed 52 previous studies involving 21,000 women found that even those who took it for less than five years raised the risk level, although it reduces once they had stopped.

The study, published in the Lancet medical journal, has led to calls for medical guidance on HRT to be updated given the “causal relationship” and the Medical and Healthcare Products Regulatory Authority (MHRA) said it would look at the findings.

The researchers said: ‘The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for five years from around age 50 have about one extra ovarian cancer per 1,000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1,700 users.

‘The findings that ovarian cancer risk is greatest in current users of hormone therapy, falls after use ceases, and varies by tumour type, strongly suggest a causal relationship – ie: that among otherwise similar women, use of hormone therapy increases the probability of developing the two most common types of ovarian cancer, and hence ovarian cancer as a whole.

‘At present, the WHO, European, and US guidelines about hormone therapy do not mention ovarian cancer, and the UK guidelines – which are due to be revised – state only that risk may be increased with long-term use.

‘The definite risk of ovarian cancer that is observed even with less than five years of use starting at around age 50 is directly relevant to current patterns of hormone therapy use, and hence directly relevant to medical advice, personal choices, and the current efforts to revise UK and worldwide guidelines.’

Hormone replacement therapy (HRT) and the risk of ovarian cancer

MHRA logo
MHRA statement in response to the study in The Lancet on the use of HRT.by Dr Sarah Branch, deputy director of MHRA’s Vigilance and Risk Management of Medicines (VRMM) Division

” Our advice has always been that the lowest effective dose of HRT should be used for the shortest possible time.

‘We will evaluate the findings of this study and its implications for shorter term use and update product information as necessary.

‘Women on HRT should have regular health check-ups and their need to continue treatment should be reassessed at least annually. Any woman on HRT who has any questions should speak to her doctor who is best placed to advise.”

Sources and more information
  • Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies, the lancet, abstract and full study PDF, 12 February 2015.
  • Short-term use of hormone replacement therapy associated with increased ovarian cancer risk, eurekalert, 12 February 2015.
  • HRT ‘increases ovarian cancer risk‘, BBC News, 13 February 2015

The association between in utero cigarette smoke exposure and age at menopause

Prenatal exposure to maternal cigarette smoke may play a role in programming age at menopause

cigarette-and-pregancy image
In this cohort of participants predominantly exposed to diethylstilbestrol, results suggest that prenatal exposure to maternal cigarette smoke may play a role in programming age at menopause.

2008 Study Abstract

Menopause onset, on average, occurs earlier among women who smoke cigarettes than among women who do not smoke. Prenatal smoke exposure may also influence age at menopause through possible effects on follicle production in utero.

Smoking information was obtained from the mothers of 4,025 participants in the National Cooperative Diethylstilbestrol Adenosis (DESAD) Project, a US study begun in 1975 to examine the health effects of prenatal diethylstilbestrol exposure. Between 1994 and 2001, participants provided information on menopausal status. Cox proportional hazards modeling compared the probability of menopause among participants who were and were not prenatally exposed to maternal cigarette smoke.

Participants prenatally exposed to maternal cigarette smoke were more likely than those unexposed to be postmenopause (hazard ratio = 1.21, 95% confidence interval: 1.02, 1.43). The association was present among only those participants who themselves had never smoked cigarettes (hazard ratio = 1.38, 95% confidence interval: 1.10, 1.74) and was absent among active smokers (hazard ratio = 1.03, 95% confidence interval: 0.81, 1.31).

In this cohort of participants predominantly exposed to Diethylstilbestrol (DES) , results suggest that prenatal exposure to maternal cigarette smoke may play a role in programming age at menopause. The possibility that active cigarette smoking modifies this effect is also suggested.

More DES DiEthylStilbestrol Resources

The Influence of Prenatal DES Exposure on the Associations of Reproductive Factors and Osteoporosis

Prenatal DES exposure may reduce osteoporosis protection

DES Follow-up Study Summary

National Cancer Inst logo image
Lifetime cumulative exposure to estrogens is protective against osteoporosis ; prenatal exposure to estrogen appears to modify these associations.

Included in this study were 5,573 women who participated in the NCI DES Follow-up Study between 1994 and 2006. Data on reproductive history and medical conditions were collected on the first follow-up questionnaire in 1994 and subsequently on the 1997, 2001, and 2006 questionnaires.

The results of the study showed that women who had fewer than 25 years of menstruation (between the start of menstrual cycles and menopause) had a higher incidence of osteoporosis when compared with women who menstruated for 35 years or more. The association of years of menstruation with osteoporosis was shown observed in both DES-exposed and unexposed women, but was stronger among women who had not been prenatally exposed to DES.

The study’s results support the hypothesis that total lifetime exposure to estrogens that occur naturally through a woman’s reproductive years protects against the development of osteoporosis. Furthermore, prenatal exposure to estrogen, in the form of DES, may reduce this protection, although we do not yet know how.

2014 Study Abstract:

Estrogen is critical for bone formation and growth in women. Estrogen exposures occur throughout life, including prenatally, and change with reproductive events, such as menarche and menopause.

The objective of this study was to investigate the association between age at menarche, age at menopause, and years of menstruation with incidence of osteoporosis and assess the impact of prenatal exposure to diethylstilbestrol (DES), a synthetic estrogen, on such associations.

Participants were 5573 women in the National Cancer Institute Combined Cohort Study of DES (1994-2006). Data on reproductive history and medical conditions were collected through questionnaires at baseline in 1994 and subsequently in 1997, 2001, and 2006. Age-stratified Cox regression models were used to calculate multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Effect measure modification by prenatal DES exposure was assessed using cubic restricted spline regression models.

Osteoporosis was the main outcome measure.

The IRRs for osteoporosis incidence with age at menarche less than 11 years and age at menopause of 50 years or younger were 0.82 (CI 0.59, 1.14) and 0.61 (CI 0.40, 0.92), respectively. Fewer than 25 years of menstruation was associated with an increased incidence of osteoporosis (IRR 1.80; CI 1.14, 2.86) compared with 35 years or more of menstruation. Associations were stronger among women who had not been prenatally exposed to DES.

Our data support the hypothesis that lifetime cumulative exposure to estrogens is protective against osteoporosis. Furthermore, prenatal exposure to estrogen appears to modify these associations, although the mechanism by which this occurs is unknown.


  • Menarche, menopause, years of menstruation, and the incidence of osteoporosis: the influence of prenatal exposure to diethylstilbestrolNCBI, PMID: 24248183, 2014 Feb;99(2):594-601. doi: 10.1210/jc.2013-2954. Epub 2013 Nov 18. Full text link.
  • NCI, DES Follow-up Study Published Papers.
More DES DiEthylStilbestrol Resources

The sweat-drenched Woman’s Guide to Enjoying an Unmedicated Menopause

Drugs? No thanks.
Perfectly safe? Forgive me for being skeptical

image of ROZ WARREN
Roz Warren is a DES Daughter who writes for the New York Times and the Funny Times.

Menopause came for me several years ago, when I was in my mid-fifties, and I can’t say that I’ve enjoyed the experience.

Women who proudly refer to their hot flashes as “power surges” are, I think, kidding themselves. But they’re not fooling me! There’s nothing fabulous about your body temperature suddenly rocketing upwards, leaving you dazed and sweating as you attempt to go about your business was if (Gasp!) nothing (Yikes!) is going on.

I work in a public library, which means that it’s not unusual for me to begin checking out your books as cool as a cucumber, and finish the transaction drenched, dizzy and red as a beet… 

Continue reading:
The sweat-drenched woman’s guide to enjoying an unmedicated menopause, by Roz Warren, a writer AND also DES Daughter

Increased Exercise associated with a Reduced Risk of Breast Cancer after Menopause

Women who exercise regularly for four years after the menopause can “rapidly decrease” their risk of breast cancer

Recent Recreational Physical Activity and Breast Cancer Risk in Postmenopausal Women

Women who exercised just moderately saw breast cancer risk drop by up to 10 per cent.

Exercise lowers risk of breast cancer after menopause” reports The Independent. This and similar headlines were sparked by a large study of postmenopausal teachers that found increased recreational activity was associated with a 10% decrease in the risk of breast cancer.

The study used questionnaires to estimate the levels of walking, cycling and sport the women did outside of work. Researchers found that women who exercised vigorously for seven or more hours each week were 25 percent less likely to develop breast cancer, compared to those who exercised less than one hour each week. Examples of vigorous activity include basketball, swimming, running and aerobics. The results were similar if women walked briskly, but there was no benefit for walking at normal pace. The results did not differ by the estrogen receptor status of the breast cancer. It also found that women who did the equivalent of walking at least four hours a week or doing sport for two hours a week had a reduced risk of breast cancer. Factors such as body mass index (BMI) did not change the results.

 Sources and More Information:
  • Recent Recreational Physical Activity and Breast Cancer Risk in Postmenopausal Women in the E3N Cohort, CEBP, June 8, 2014.
  • Recreational Physical Activity and Leisure-Time Sitting in Relation to Postmenopausal Breast Cancer Risk, CEBP, August 1, 2013.
  • Television Viewing and Time Spent Sedentary in Relation to Cancer Risk: A Meta-Analysis, JNCI, March 14, 2014.
  • Exercise may cut breast cancer risk, study finds, Edited by NHS Choices, analysed by Bazian.

Women and the Crisis in Sex Hormones

Complete handbook by Barbara Seaman, published in 1981, about birth control, DES, menopause, remedies and more…

Women and the Crisis in Sex Hormones book cover image
Complete handbook published in 1981 about birth control, DES, menopause, remedies and more…

Barbara Seaman, author of The Greatest Experiment Ever Performed on Women, previously wrote a book entitled The Doctor’s Case Against the Pill, which was almost single-handedly responsible for calling the attention of Senator Nelson and his committee on drugs, as well as that of the public, to the dangers of hormone contraceptives for women, as well as to the indifference and perhaps denial of the medical profession generally. Now, in the Women and the Crisis in Sex Hormones book coauthored by her husband, a psychiatrist and psychopharmacologist, the subject is extended to a comprehensive examination of the entire contraceptive field.

Written with a biting and sardonic humor at times, it is a remarkable piece of investigative reporting, comprehensive enough to serve as a reliable reference work. It considers alternatives to hormonal contraception, including the diaphragm, cervical cap, intrauterine device, foam, current rhythm methods, sterilization, abortion, the condom, vasectomy, and a pill for men. It considers menopause and the use of hormones in relation to it.

Sources JAMA 1978;239(20):2179. doi:10.1001/jama.1978.03280470091039

The first chapters of this book are about DES history.

More DES DiEthylStilbestrol Resources
On Flickr®

The Greatest Experiment Ever Performed on Women

Barbara Seaman book – tracks the well-intentioned discovery of synthetic estrogen through the unconscionable and misleading promotion of a dangerous drug: DES

Exploding the Estrogen Myth

The Greatest Experiment Ever Performed on Women
Exploding the Estrogen Myth

With the ardent tone of a close friend, Barbara Seaman draws on forty years of journalistic research to expose the “menopause industry” and shows how estrogen therapy often causes more problems—including breast cancer, heart attack, and stroke—than it cures. The Greatest Experiment Ever Performed on Women tracks the well-intentioned discovery of synthetic estrogen through the unconscionable and misleading promotion of a dangerous drug.

Barbara Seaman’s groundbreaking book traces the history of estrogen use from its early purveyors, including a well-meaning British doctor who lost control of the marketing of DES and therefore inadvertently led to the DES baby crisis, to Nazi experimentation with women and estrogen, to the present, and looks at how an experiment of this proportion could have been conducted without oversight, intervention, or real knowledge as to what its effects would be.

Barbara Seaman turns up essential, often shocking, information that should have been part of public awareness but, only now, is coming to light.

Read Amazon reviews – GoodReads reviews.

More DES DiEthylStilbestrol Resources