Twenty- four years ago, I became chair of Tall Girls Inc in Australia. Interestingly, our story has now been given coverage on the Dutch TV program ‘Radar’. Footage from Insight (SBS TV 1997) was used to provide the historical context and discussion as to what happened to us, why, and what are the long- term effects? Women in Holland are now expressing their own concerns which mirror exactly those we expressed all those years ago.
In 2004 a paper on the long-term effects on fertility was published in The Lancet, by Dr. Alison Venn et al.
The conclusion was that treated Tall Girls, whether exposed to DES or EE, were at significant risk of experiencing infertility or were sub fertile.
This result was also delivered to an International conference of Paediatric Endocrinologists and Endocrinologists held at the time in Melbourne. Tall Girls Inc was reassured that these conclusions would bring to an end this form of unnecessary cosmetic endocrinology, worldwide.
How wrong were we!! We now learn that in Holland this treatment did not stop until 2012!!
This treatment, more than 24 years later, is now receiving attention in Holland. Women are sharing their stories and expressing their concerns about their health problems, as we did in Australia. RADAR, a program on the Dutch public broadcaster TV network, has covered the story providing an opportunity for a discussion and for women to tell their stories, network and take action.
What is very clear, is, there is an urgent need for further research so that the plight of treated women, whatever their country of origin, is acknowledged and understood and not dismissed.
RADAR program on 22.02.21
Radar Translation from 22/2/21
“In 2012 it became known that growth inhibitors can cause infertility, among other things. At that time I was engaged in IVF treatments myself. Unfortunately, I turned out to be infertile and was already at the beginning of the menopause at the age of 35” writes 'someone who prefers to remain anonymous’ in an email to Radar.
It's too painful. It has radically changed her life.
“I'm probably not the only one who has been bothered by this. It has had quite an impact on my life, and on my husband's, of course. Do you know if anything is known?”
Her question becomes the starting point of a search.
The Dutch are among the tallest people in the world. We now find this very normal, but this has been different for a long time. We are going back in time. In the 1960s, Australian paediatrician Dr. Wettenhall was experimenting with the hormone DES, which was to be discredited ten years later.
What is diethylstilboestrol (DES)?
DES is the abbreviation for 'diethylstilboestrol' and is prescribed in the Netherlands between 1947 and 1976 to pregnant women with the aim of preventing miscarriages. In 1971, the FDA issued a warning that doctors should no longer prescribe DES to pregnant women. The warning was based on a study identifying DES as the cause of a rare vaginal cancer in so-called DES daughters.
It is not possible to determine whether, and on what scale, DES was also prescribed for the indication 'constitutionally tall stature' in the Netherlands. One publication as part of a student project concludes that it is 'unlikely' that DES was used in the Netherlands. The authors wrote a 'summary' based on student reports. For this summary, they spoke to several doctors and wrote: "The doctors all state that it is very unlikely that this drug has been used for this indication."
But at that point, in the 1960s, it seemed to paediatricians in Australia that it would be an appropriate treatment for girls at risk of growing too tall. There, as Dr. Wettenhall in 1975, described, “concern about tall stature”. Whose 'concern'? The social idea seemed to be: tall girls are less likely to find a man. Women should not exceed a man in height.
Growth plates close faster due to treatment
It was a different time for women. As such, a medical treatment was devised for healthy young girls. The female synthetic hormones in high doses ensure that the growth plates close more quickly, enter puberty more quickly and accelerate growth. 450 girls participated in Dr. Wettenhall’s initial study. The girls in the study took high doses of synthetic female hormones (Diethylstilboestrol) for more than two years.
The results were published in 1975. The conclusion was that there was a 3- 5 cm reduction in height but caution is advised. Possible side effects should be taken into account.
Dutch Annelies Blok went with her parents to a doctor in Amsterdam in the late 1960s and early 1970s. All the women in her family are tall and they had great difficulty with that.”My parents wanted the best for me. It was a different time. You do what your parents say. I was a child, I didn't really have a choice.”
She swallowed the pills she remembers as 'Stilbestrol'. For months, she does not know exactly for how long. Puberty was difficult, she had bleeding in three out of four weeks per month. Mentally it is tough. She felt lonely.
Dosage of hormones much higher than in contraceptive pill
The type and brand of female hormones prescribed in the Netherlands appears to be difficult to identify. Just like the Australian girls, Annelies has taken Stilbestrol, but most women who have been treated in the Netherlands have been treated with ethinyl estradiol, another female synthetic hormone that we also find in the contraceptive pill. However, the dosage for the indication 'constitutionally tall stature' is much higher than in the contraceptive pill. The dosage of 200 micrograms per day, that amount is equal to almost 7 contraceptive pills per day or one morning after pill per day. The young girls take the pills for weeks, months or years. Daily.
We asked that women who have taken hormones at a young age in order not to grow tall contact the program Radar. 64 women respond. The women were treated in the period from 1970 to 2011. The youngest woman is now 22 years old and the oldest is 63 years old. We asked them about the side effects and experiences. Some women report reduced fertility, IVF treatments, long courses with several miscarriages. Others are still young and not yet trying for children or do not want to have children. Still other women report no fertility complaints.
Some do have other complaints, such as specific forms of cancer in which they wonder: could this have been related to the hormone treatment?
Depression, binge eating and behavioral problems
Annelies Blok developed uterine cancer in 1999. "I felt that the hormones that I had taken as a young girl might have had something to do with the cancer. But where to start? My doctor at the time no longer had the file. There was little interest in investigating this further.”
She made an appeal in the Margriet to get in touch with other women. Some women do not know exactly what they took. It was long ago for them. They have grown up and often want to leave the whole chapter behind.
Through a search, Annelies comes into contact with the Australian, Janet Cregan-Wood. Janet is one of the girls from Dr. Wettenhall study in Australia. Her mother took her to the doctor – and was told there were few side effects, other than weight gain. She was prescribed a high dose of stilbestrol at the age of 11 and 12.
“As a young girl you suddenly get a libido, my body quickly changed from a girl into a woman.” She suffered from severe depression, binge eating and behavioural problems for which she was under psychiatric treatment. But what remains with her throughout life is: she received medical treatment when there was nothing wrong with her. She did not feel accepted, and thought she was not 'normal' because she was offered this medical treatment. "This feeling remains, it is etched into who you are."
Janet has two children after five miscarriages
After five miscarriages, Janet eventually has two children. “I was one of the lucky ones” she says.
When the Australian ‘Tall Girls’ met they start to exchange experiences. It was striking that many women were struggling with fertility problems. They exchanged stories and met regularly. They wanted answers from their doctors, from their government. The fertility problems and the hormone treatment they shared, brought them to believe that “this can't be a coincidence, can it?”
Janet founded Tall Girls Inc in 1997. The women received a lot of media attention in Australia and finally achieved what they were fighting for: world first epidemiological research into the long term effects of their treatment. The conclusion: high dose hormone treatment is associated with reduced fertility in later life.
The results were published in October 2004 in The Lancet.
Lancet study does not differentiate between DES and ethinyl estradiol (EE)
In the Lancet study, no distinction was made between DES and ethinyl estradiol (EE) for the effect on fertility. Prof Dr.Alison Venn: "We saw clear evidence that fertility was lower and different in the women treated with hormones." In addition, the researchers found reduced fertility in both women treated with DES and the women treated with EE.
Alison Venn's study is not the only study to investigate the consequences for fertility. In the Netherlands, a number of paediatric endocrinologists investigated this. Many names keep coming back, it is a subspecialty, a handful of paediatricians are researching this. To be prescribed the hormones you have to be referred to a specialist in a hospital, often academically. In 1995 Dutch researchers wrote : “subfertility cannot be ignored”, even though the results are 'difficult' to interpret.
Three years later, in 1998, research was conducted again. Possible long-term effects are considered, but 'definitive conclusions cannot be drawn'.
Study is the reason for Dutch research
Alison Venn's Australian study is clear in the conclusion. Were the Dutch researchers not aware of this study? Yes, says Emile Hendriks, at that time, in 2004, still a medical student when Alison Venn's study appeared in the Lancet. Indeed, it is the reason Hendriks participated in a Dutch study in 2005.
Nevertheless, in 2005 Dutch paediatricians argue in the Dutch Journal of Medicine (NTVG) that growth-limiting treatment can be considered with high doses of sex hormones in girls if a final height is predicted of 185 cm for girls and more than 205 cm for boys. They refer to the Dutch study from 1998 when they write here: "A follow-up study of 10 years showed no influence on fertility and the development of malignancy."
It is difficult to find out exact numbers for treated women
Through the Australian Janet we come into contact with Chris Cosgrove and Susan Cohen, authors of the book: Normal at Any Cost: Tall Girls, Short Boys.
Chris says that treatment occurred in the US, on thousands of women with synthetic sex hormones in high doses to limit height. It is not clear how many women have been treated in the US. Chris reports that most women have been treated with DES and to a lesser extent ethinyl estradiol (EE), starting in the 1940s and 1950s. Exact figures are difficult to obtain…
Figures from SFK
We also encounter this ourselves. The Stichting Pharmaceutische Kengetallen was unable to provide indications as to prescriptions that were prescribed. We ask about the number of hormone prescriptions in combination with age. They reported that in 1 year, in the year 2010: ethinyl estradiol 0.01 - 0.05 mg was prescribed more than 700 times by Dutch community pharmacies. "We estimate that this was used by about 500 girls."
“In 2015, the number of prescriptions dropped to almost 150, whereby we estimate that there are more than 100 girls who received this drug. It was prescribed for girls between the ages of 9 and 14.” (source: SFK at the request of Radar)
This seems difficult to compare with the estimate made by Dr. Emile Hendriks and his co-supervisor Prof Dr. Drop that between 1968 and 1999, between 1,500 and 2,000 girls would have been treated.
Which brand and which manufacturer is it?
But what brand it was, what manufacturers brought this product to market? We requested information from the Medicines Evaluation Board. The name 'Lynoral' emerges. Lynoral has been registered since 1990 for the 'treatment of metastatic (metastatic) breast cancer'. The Lynoral product information states: 'psychological side effects can occur in high doses and long-term treatment' and "Caution is advised in its use in adolescents." And "So far it has not been proven that ethinyloestradiol has teratogenic [malformations in the unborn child"].
Lynoral off-label used for height growth in 'constitutionally tall girls'
In 2001, the Organon company in Oss decided to withdraw the product from the market. Only then did it appear that Lynoral was also used off-label by paediatric endocrinologists for stunting height in 'constitutionally tall girls'. Because the drug is - according to the MEB - difficult to prepare by pharmacists, was to be reintroduced on the market in 2002 for the indication for which it was also prescribed off-label: constitutionally tall stature.
From 2002 to 2012, the Lynoral product characteristics state: "Long-term effects on reproductive function as yet unknown." In 2015, the same drug will be available under the name Acelyn. In 2012, the Dutch paediatrician Emile Hendriks will received his doctorate on this subject. The subject received considerable national attention. Afterwards, the guidelines were adjusted and, according to Hendriks himself, hardly any hormones were prescribed for growth inhibition.
After 2012, the Lynoral package leaflet was updated: 'The use of Lynoral may have an effect on fertility. This means that there could be a higher risk that you will not be able to get pregnant or will be more difficult. Discuss this with your doctor before starting treatment with Lynoral.
Do you also have experience with this?
Let us know: Experience with growth inhibitors?
RADAR program on 1.03.21
Many reactions after the broadcast about growth inhibitors, what is the next step?
Translation
Radar received more than 500 responses to our broadcast on growth inhibitors on 22 February. The stories are poignant, diverse and shocking. Some women are only now recognizing that their complaints about reduced fertility could be due to the hormone treatment.
In our broadcast, we showed that girls who used to take growth inhibitors in order not to become too tall, may experience reduced fertility later in life.
We asked for experiences related to the taking of growth inhibitors to be sent into the program. A selection of the responses we received:
“Listened and watched with tears in my eyes during the broadcast. Heard my story and would have loved to know these things sooner. During the IVF treatments I asked several times to different doctors if the growth hormone treatment could be the cause of my infertility and this was always answered in the negative. In my heart I always knew that the growth hormones had to do with this. And I really want to know what may still be waiting for me. '
“It never bothered me, but it was shocked after seeing the broadcast. I am mainly looking for more information.”
Almost everyone who reports to Radar wants to join a foundation, wants more information, more research and to be kept informed of further developments. Some women have a need for contact with fellow sufferers. Others want to take legal action.
As a result of our broadcast, women recognize where their complaints and side effects may have come from: “Now finally since tonight with the broadcast confirmation that I have experienced all these years”, someone says.
Below you will find more reactions to our broadcast, divided by category.
Unwanted childless (remained)
Women emailed Radar about their early menopause and how they became infertile and unwanted childlessness. There are those who have had many miscarriages:
“Repeated miscarriages and not (yet) a full-term pregnancy”, is a response.
Some women have gone on a long journey of different IVF treatments, sometimes without results:
“Infertile, had an IVF route afterwards in 2009 and 2011 had an ectopic pregnancy in which both fallopian tubes were removed. My uterus was removed in 2017 due to heavy menstruation.”
“After 7 years I stopped contraception to get pregnant. Many miscarriages followed. Reason for this is not known; to my great sorrow, I never had children."
In the middle of a fertility process
Then a group that emails Radar because they are now in the middle of a fertility process, here are some responses:
“Have been trying to conceive for five years now. Uterus surgery in Belgium, 10 times IUI and 1 time IVF, so far no result.”
'”Not in the past, never bothered. Manage now not to get pregnant (and remain). Start with IVF.”
Not ready to have children yet and wonder what awaits me in the future.
The group of women who are not yet in the process of having children, but who have taken growth inhibitors, are concerned and wonder: what can I still expect?
“I am now 22 and I am sorry that I do not know whether I will be able to have children later or whether I might get other complaints. Young girls aged 10-15 are often far too young to make such a decision with potentially major impact.”
“I am now 25 and in the prime of my life. I have a wish to have children, not yet in the short term, but in a while. It's me all over known growth inhibitors provide infertility. This knowledge leaves a mark on my vision of the future with regard to children: should I start early, should I get tested, what if I don't succeed right away?”
Other side effects
In addition to infertility and reduced fertility, women also report other complaints such as:
- Hair loss
- Psychological complaints (depression, anxiety)
- Muscle cramps
- Endometriosis (severe form, surgery)
- Oedema in legs
- Many menstrual problems / Disturbed menstruation (including breakthrough bleeding)
- Bladder cancer
- Back and joint complaints
- Fatigue
- Hormonal complaints, mood swings, anger, etc.
- Overweight since using growth inhibitors
- Menopause complaints
- Intestinal tumours
- Chronic headaches
- Troubled cervix cells
- Frozen Shoulder
With a lot of effort eventually got pregnant
Some women report how they spent years trying to have children:
“I had surgery on an adhered ovary at the age of 30. The ovary was then removed. I then put the idea of trying to get pregnant out of my system. Years later, the wish overcame and I wanted to try it anyway. I did get pregnant, but that turned out to be a miscarriage. After that I did not get pregnant any more. As a miracle I became pregnant in another relationship at the age of almost 41 with a now 8-year-old son. It's only now that I've seen the Radar episode that I wonder if there have been any side effects from the hormones!”
“Infertility. Finally, after several IVF treatments mother of two daughters. This was a tough mental time”
“Reduced fertility. After six times IUI / KI, two IVF treatments and five years of muddling happily got pregnant. I was 26 when I stopped taking the pill, so not exactly an older mother. Our daughter was born in 2003. In 2012 my liver was full of tumours. Diagnosis of liver adenomas. These arise under the influence of estrogenic hormones. About 40 in one million people have this condition and the condition is not known in families. I have also been diagnosed with endometriosis. The endometriosis is located in the uterine wall. My seventeen-year-old daughter now also has this diagnosis. I do not know whether this is related to the growth inhibitors. The condition is also not known in families.”
No side effects - if known - but what's in the future?
The last group to respond are women who have not yet experienced any side effects, but wonder if there will be any further side effects. Or what effect the hormones have on their own children: “I myself have had few side effects. My weight gain disappeared when I stopped taking the medication. I got pregnant without any problems and gave birth to two healthy children. Only: I would like to know when my hormone treatment could have any effect on them (I have a son and a daughter).”
“I would like to know if this has done anything to my body, I am very shocked by the dose of hormones. How would it be with my uterus / ovaries?”
Then another response from a parent who mentions an alternative to growth hormones:
“Our daughter is currently in the growth braking process. Not with hormones, although that has still been discussed, but with piercing the growth plates in the knees. But we are yet to see what the results are, and what the consequences are in later life. It was reported by the doctor that she will get really ugly scars on the knees, but no pictures can be found anywhere. She is just 10 and 165 cm tall with a prognosis above 190 cm and she absolutely does not want that. But you can't find information anywhere to make an informed choice. So, the alternative to hormones is not really transparent either.”
Personal injury lawyer John Beer responds
John Beer answers the responses we received and answers questions about this topic, including about the plans for establishing a foundation.
More expert responses
The Medical Centre for Children and Professor Joop SE Laven, Professor of Reproductive Endocrinology and Infertility, also responded to our item.
Reactions from political parties and ministry
We have asked a number of political parties for a response. The SP responded in the studio and has sent a written response. VVD, D66, CDA, GroenLinks, Christenunie and PvdA have informed us that they were not able to respond due to the pressure.
The Ministry of Health, Welfare and Sport has sent us a response.
How are Anniek and Lynn doing?
How are things now with Anniek and Lynn, from the previous broadcast about growth inhibitors ? They tell their story in detail in this article .
Anniek and Lynn also tell more on our Instagram page.
Do you have experience with growth inhibitors?
Would you also like to leave a comment for the editors, or share your experience? And are you interested to connect you to a foundation that will deal with this issue? Let us know..
