hormones matter

Women in Clinical Trials

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Do Hormones Matter with Clinical Trials Research?

I am repeatedly struck by the avoidable ignorance that surrounds this industry. Women’s hormones are considered a fringe science by many, despite the fact that hormones modulate all bodily functions and impact all aspects of pharmacokinetic and pharmacodymanic response, the key variables evaluated in clinical trials research. Repeatedly, we face the assumption that hormones make no difference to women’s health – quite ironic since simultaneously hormones are blamed for everything from migraines to mental health.

And then there is the long held notion that we don’t need any more data in women’s health – quite striking considering only 30% of Ob/Gyn clinical practice guidelines are based on data. Just the other day, a well-positioned female physician, one of the fewer than 4% female healthcare executives, argued that while what we doing was interesting,  it was unnecessary because the 1993 Gender Guidelines ‘mandated’ women be included in clinical trials.

Perhaps some history is in order. Until 1993, women of ‘childbearing potential’ were prohibited from participating in clinical trials research. This means that all of the drugs developed before 1993 (most are still being used today) were not tested on women; any potential dosing differences, sex- specific side-effects could not be found until after the drug reached the market and even then it was and is difficult to ascertain because sex-specific analytics were not, and are still not, routinely performed. This makes proving sex-based adverse events all but impossible.

In 1993, thanks in large part to efforts of the first large group of women to enter the US Congress (women in Congress matter); the FDA removed its prohibition against women with childbearing potential participating in clinical trials. The regulations, however, were not established until 1998 and what was implemented, though an improvement over the earlier prohibition of women in clinical trials was less specific than the original guidelines and resulted in less than satisfactory results. When those regulations are evaluated alongside industry trends over the last decade, it becomes abundantly clear why women suffer disproportionately from adverse events compared to men and why everyone in the healthcare industry should be concerned.

From Proposed Guidelines to Regulation

The 1993 guidelines recognized that women might process and react to drugs differently than men (indeed they do and this has been shown repeatedly) and therefore, it was recommended that pharmacokinetic studies be done to evaluate the difference in drug absorption, distribution, metabolism and excretion. It was further recommended that menstrual status, hormonal supplementation (oral contraceptives, HRT and the like) be evaluated.

The FDA was quite clear in its ability to mandate these changes – there was none.  Indeed, all that was possible was suggestion.

The agency recognizes that this change in FDA policy will not, by itself, cause drug companies or IRBs to alter restrictions they might impose on the participation of women of childbearing potential. We do not at this time perceive a regulatory basis for requiring routinely that women of childbearing potential be included in particular trials, such as phase 1 studies. However, careful delineation of drug effects by gender is expected by the agency and the FDA is determined to remove the unnecessary federal impediment to the inclusion of women at the earliest stages of drug development.  The agency is confident that the ethical, social, medical, legal and political forces will allow greater participation of women at the earliest phases of drug development.

So, the FDA was confident that ethical and social pressures would convince pharmaceutical companies to do the right thing. How well has that gone? The guidelines also indicated that it was not necessary to include women in phase 1 or 2 trials because there was no evidence to suggest sex differences in drug effectiveness:

Because documented demographic differences in pharmacodynamics appear to be relatively uncommon, it is not necessary to carry out separate pharmacodynamic – effectiveness studies in each gender routinely.

To summarize, data were never collected in the first place to suggest sex-differences might exist (remember before 1993, women were prohibited from participating in clinical research) and because there were no data to suggest a sex-differences, there was no need for additional data – makes perfect sense to me.

Fortunately, the National Institute of Health (NIH), the federal funding agency for health-related research, took the reins with a clear mandate – no funding unless the study included women in clinical research.  The NIH Revitalization Act of 1993, followed by updates and regulations in 1994, 2000 and 2011, mandated that all NIH funded clinical trials have sample sizes adequate to support ‘valid analysis’ of gender and racial subgroup effects. Unfortunately, however, NIH-sponsored clinical trials represent only 20% of all clinical trials. The remaining 80% are sponsored by pharma and fall under the FDA’s guidelines. And even though, by all accounts the NIH has done substantially better than the FDA, a recent report by the National Heart, Lung and Blood Institute (NHLBI) – a sub agency of the NIH, found that in clinical trials between 1997 and 2006 where the outcome of the study was stroke, myocardial infarction or death found that women represented only 27% of trial participants and only 13-19 of the studies included sex-based analyses.

Back to the FDA Regulations

In 1998 and 2000, the FDA officially instituted the Guidance for Industry, requiring all new investigation drug (IND) and new drug application (NDA) submissions include data on trial participation, efficacy and safety, be presented by age, race and sex. A report in 2001 by the General Office of Accounting (GAO) (no further GAO reports could be found on this topic) evaluated the success and failures of the gender guidelines. It wasn’t pretty:

The 1998 regulation has the force of law, but it is less specific than the 1993 guidance. The regulation required that safety and efficacy data already collected be presented separately for men and women in new drug application summary documents. It does not include criteria for determining the number of women to be included in clinical studies, nor does it require any analysis of the data presented. The 1998 regulation also requires the tabulation of the number of study participants by sex in investigational new drug annual reports. The regulation enacted in 2000 allows FDA to halt research programs for drugs for life-threatening conditions if otherwise eligible men or women are excluded from participation in studies based solely on their reproductive potential, but it does not require inclusion of any particular number of men or women.

How well did the FDA do in meeting and enforcing the guidelines? According to the GAO:

  • NDA and IND summary documents and annual reports often failed to meet the data presentation requirements
  • 30% the new drug application summary documents submitted to FDA by drug sponsors did not fulfill the requirements for the presentation of available safety and efficacy outcome data by sex
  • 39% of IND annual reports did not include demographic information
  • The FDA has the authority to suspend proposed research for life-threatening conditions if men or women are excluded, but has not yet done so

As a result of the non-enforcement, the GAO found that although the number of women in clinical trials now averaged 52%, most were enrolled in later stages of the trial. Women represented only 22% of early phase clinical trials. This is where most of the safety and dosing considerations are determined.

Finally, and perhaps the most troubling aspect of this report was that, the FDA had no procedures in place to evaluate, manage or enforce the regulations. As a result, they had no way of knowing whether women were included in the trials in sufficient numbers or whether the medications or devices gaining approval had gender-specific safety issues.

What does this mean?

For all drugs and devices approved before the 1998-2000 regulations and likely many years after, the safety and efficacy data were lacking for women. Despite the 52% female participation number that is bandied about as proof positive that women are represented sufficiently in clinical trials, that number reflects later phase trials, after safety and efficacy parameters are established. In the early phase trials, the number of female participants remains at a paltry 22%. Today, when large women-only (Women’s Health Initiative and Women’s Health Study) research are removed from the tabulations, the mean proportion of women included in all clinical trials hovers around 27%.

Most recently, the Institute of Medicine (IOM) Committee of Women’s Health Research reports a continued lack of

taking into account of sex and gender differences in the design and analysis of studies, lack of reporting on sex and gender differences, has hindered identification of potentially important sex differences and slowed the practice in women’s health research and its translation into clinical practice.

And although the IOM reports that the most progress has been made in cardiovascular research, the NHLBI and Cochrane Reports suggest otherwise. The NHLBI found female participation hovering around 27% in certain cardiovascular trials and Cochrane Reports found that out of 258 clinical trials, only 196 included women and only 33% of those reported sex or gender analytics.

Cardiovascular disease is the most common cause of death in American women and in recently recalled medications for heart disease there were disproportionately higher fatalities and serious adverse events in women than in men.

With high risk cardiac devices, a recent review of FDA pre-market approved devices from 2000 – 2007 (78) found significant gender bias in sampling and data reporting and significant lack of sex-specific safety data.

  • FDA summaries did not report gender data in 28% of studies examined
  • For studies reporting gender distribution, 67% of the participants were men

So, the suggestion that additional data in women’s healthcare are not needed is unquestionably false and dangerously ill-informed. The notion that hormones, which regulate every aspect of pharmacokinetics and pharmacodynamics are an irrelevant and a fringe science, is ignorant bordering in negligent. It is time for women to stand up and demand inclusion and analytics by sex for all drugs and devices.

Postscript: NIH Update 2014

Since this article was first published in February 2013, the NIH has made inroads towards more thorough assessment of the role of sex in basic, pre-clinical research. Recognizing the almost total reliance on male animals and cells in preclinical research obscures key sex differences that should guide clinical studies, the NIH instituted new guidelines in October 2014

…that require applicants [for NIH grant funding] to report their plans for the balance of male and female cells and animals in preclinical studies in all future applications, unless sex-specific inclusion is unwarranted, based on rigorously defined exceptions. 

It remains to be seen how rigorously these new guidelines will be enforced and whether they will impact health research in any discernible way.

Postscript: Update 2019

From a recent 10 year follow-up study assessing sex-inclusive research practices of journal articles published within nine of the biological disciplines, including pharmacology, researchers found some improvement in most of the disciplines, except pharmacology. Compared to 2009, where only 29% of the studies reviewed included male and female subjects, in 2019, 49% included both. In contrast however, pharmacology trended downward with only 29% of articles reporting the use of both sexes in 2019 compared to 33% in 2009.  Nevertheless, even though more women were included in more research studies across the disciplines reviewed, few researchers thought it was important to analyze sex based differences. Indeed, of the 49% of journal articles that included both sexes in 2019, only 42% analyzed data by sex, compared to 50% in 2009. Ironically, in pharmacology although the total number of women decreased in studies during this time period, analyses of sex based differences was more frequent increasing from 19% in 2009 to 48% in 2019.

Overall, it appears that we have yet to make much progress.

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This article was first published in 2013. 

Merry Christmas, Happy Holidays, and A Wonderful New Year

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Wishing you and yours a wonderful holiday season and a happy, healthy, New Year.

A special thanks to all of our writers, contributors and readers who have helped us grow.

Over the next week, we’ll be on an abbreviated publishing schedule to give our writers time with their families. Hormones Matter will return after the New Year with lots of great articles and exciting new features.

Happy Holidays.

 

 

Hormones Matter’s Top 100 Articles for 2014

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Happy New Year, everyone. What a remarkable year it has been. Hormones Matter reached its one millionth read in October and continues to grow month after month. Since inception, we’ve published almost 800 articles, many are read by thousands of readers every month. A million reads is a huge milestone for us. We’re a small operation with no funding run by passionate volunteers. We publish on a range of complicated, and often, not so pleasant health topics; topics that other journals would not consider addressing. Breaking through and finding readers in today’s heavily sponsored, content advertising and clickbait publishing environment is difficult, but we did it. Kudos to all involved.

Our success is thanks to our fantastic crew of writers, all volunteers, none professional, who spend countless hours researching complex medical topics, making connections, identifying unconventional therapeutic opportunities and bringing to light, what are often, invisible illnesses. Without these incredibly talented and compassionate individuals, Hormones Matter would not exist.

Before we begin the new year in earnest, let us take a moment to thank all of the writers of Hormones Matter. Below are the articles and authors who made the top 100 list for 2014. Congratulations and thank you. Your work makes a difference.

Hundreds of articles didn’t quite make this list, but they are no less important. In fact, the top 200 articles on this site, each have over 1000 reads.

If you haven’t read these articles, it’s time to do so. If you like them, share them and share our site so we can continue to grow.

Since we are run by volunteers and unfunded, feel free contribute a few dollars to cover the costs of maintaining operations. Crowdfund Hormones Matter. Every dollar helps.
If you’d like to share your health story or join our team of writers: Write for Us.

Hormones Matter Top 100 Articles of 2014

Article Title and Author Reads
1. Post Hysterectomy Skeletal and Anatomical Changes -WS 56,064
2. Sex in a Bottle: the Latest Drugs for Female Sexual Desire – Chandler Marrs 51,241
3. Endometrial Ablation – Hysterectomy Alternative or Trap? -WS 47,561
4. Gardasil Injured – Dollie Duckworth 24,240
5. Connection between Hypothyroidism and PCOS – Sergei Avidushko 23,361
6. Adhesions: Cause, Consequence and Collateral Damage – David Wiseman 17,841
7. In the ER … Again! Heavy Menstrual Bleeding -Lisbeth Prifogle 14,886
8. Is Sciatic Endometriosis Possible? – Center for Endometriosis Care 12,939
9. Gardasil: The Controversy Continues – Lisbeth Prifogle 12,434
10. A Ruined Life from Gardasil – Tracy Andrews-Wolf 11,703
11. Endometriosis: A Husband’s Perspective – Jeremy Bridge-Cook 11,674
12. Skin Disorders post Gardasil – Chandler Marrs 11,200
13. One Less After Gardasil -Roxie Fiste 9,795
14. Five Years After Gardasil – Ashley Adair 9,753
15. Endometriosis and Risk of Suicide -Philippa Bridge-Cook 8,459
16. I Wanted to Die Last Night: Endometriosis and Suicide – Rachel Cohen 7,585
17. Endometriosis After Hysterectomy – Rosemary Finnegan 7,333
18. A Day in the Life of Alexis Wolf: Six Years After Gardasil – Tracy Andrews- Wolf 7,037
19. Love Hurts – Sex with Endometriosis – Hormones Matter 7,003
20. Wide Awake: A Hysterectomy Story – Robin Karr 6,838
21. Mittelschmerz – what should you know – Sergei Avdiushko 6,585
22. Adverse Reactions, Hashimoto’s Thyroiditis, Gait, Balance and Tremors – Chandler Marrs 6,479
23. My Battle with Endometriosis and Migraines – Angela Kawakami 6,479
24. Hysterectomy or Not – Angela’s Endometriosis Update – Angela Kawakami 6,393
25. Sexual Function after Hysterectomy – WS 6,278
26. Before and After Gardasil – Nicole Alexandra 6,075
27. Digging Deeper into Mitochondrial Dysfunction – Chandler Marrs 6,069
28. Post Gardasil Dysautonomia: Nina’s Story – Francine Pugliese 5,937
29. Cyclic Vomiting Syndrome and Mitochondrial Dysfunction: Research and Treatments – Philippa Bridge-Cook 5,900
30. Thyroid Disease Plus Migraines – Nancy Bonk 5,615
31. Mommy Brain: Pregnancy and Postpartum Memory Deficits – Chandler Marrs 5,563
32. Vitamin D3 and Thyroid Health – Susan Rex Ryan 5,542
33. How Hair Loss Changed My Life – Suki Eleuterio 5,433
34. Adenomyosis – Philippa Bridge-Cook 5,209
35. Is Prenatal Dexamethasone Safe: The Baby Makers’ Hubris – Chandler Marrs 5,074
36. Porn Brain – A Leading Cause of Erectile Dysfunction – Chandler Marrs 5,023
37. The Gardasil Cervarix HPV Vaccine Survey – Chandler Marrs 4,940
38. Hysterectomy: Impact on Pelvic Floor and Organ Function – WS 4,534
39. Personal Story: My Thyroid Cancer – Myrna Wooders 4,018
40. Brain Connections between Thyroid Disease and Migraine – Chandler Marrs 3,888
41. Are You Vitamin B12 Deficient? – Chandler Marrs 3,864
42. Thiamine Deficiency Testing: Understanding the Labs – Derrick Lonsdale 3,797
43. Endometriosis – Not Just a Reproductive Disease – Philippa Bridge-Cook 3,791
44. Endometriosis, Adhesions and Physical Therapy – Philippa Bridge-Cook 3,699
45. Pain After Endometriosis Excision Surgery – Philippa Bridge-Cook 3,667
46. Endometriosis and Adhesions – Angela Kawakami 3,619
47. Bleeding Disorders Overlooked in Women with Heavy Periods – Philippa Bridge-Cook 3,503
48. Cyclic Vomiting Syndrome – Philippa Bridge-Cook 3,477
49. The Fluoroquinolone Time Bomb – Answers in the Mitochondria – Lisa Bloomquist 3,379
50. The High Cost of Bad Birth Control: Yasmin and Yaz Lawsuit News – Chandler Marrs 3,333
51. Lupron Side Effects Survey – Chandler Marrs 3,289
52. Gardasil Autopsies Reveal Cerebral Vasculitis – Chandler Marrs 3,228
53. Does Maca Powder Reduce Menopausal Symptoms? – Amy Roost 3,019
54. DES – The Drug to Prevent Miscarriage Ruins Lives of Millions – DES Daughter 3,009
55. Anti-NMDAR Encephalitis and Ovarian Teratomas – Chandler Marrs 2,956
56. Angela’s Endometriosis Post Operative Update – Angela Kawakami 2,945
57. Recurrent Miscarriage – Philippa Bridge-Cook 2,855
58. Lupron and Endometriosis – Jordan Davidson 2,844
59. Pap Smears Saved my Life: Cervical Cancer After Gardasil – Zoe Vickers-Kerr 2,788
60. Endometriosis and Pregnancy at a Glance – Center for Endometriosis Care 2,771
61. Post Gardasil POTS and Thiamine Deficiency – Derrick Lonsdale 2,745
62. Eating Whole Foods and Uterine Health – Eve Agee 2,708
63. Lupron or Laparoscopy to Diagnose Endometriosis? – Rosalie Miletich 2,676
64. Is it Endometriosis? – Rosalie Miletich 2,668
65. PCOS, Pregnancy, Metformin and Vitamin B12 Deficiency – Chandler Marrs 2,644
66. Please Folks – Migraine Is NOT A Headache – Nancy Bonk 2,638
67. Cipro, Levaquin and Avelox are Chemo Drugs – Lisa Bloomquist 2,592
68. A Call for Improved Thyroid Treatment Options – ThyroidChange 2,493
69. Thiamine Deficiency and Aberrant Fat Metabolism: Clues to Adverse Reactions – Derrick Lonsdale 2,486
70. Fluoroquinolone Antibiotics Associated with Nervous System Damage – Lisa Bloomquist 2,470
71. Eating and Endometriosis: My Story – Angela Kawakami 2,456
72. An Often Overlooked Cause of Fatigue: Low Ferritin – Philippa Bridge-Cook 2,453
73. Glabrata – A Deadly Post Fluoroquinolone Risk You’ve Never Heard About – Debra Anderson 2,403
74. Fluoroquinolones 101 – Antibiotics to Avoid – Lisa Bloomquist 2,383
75. Endometriosis and Adhesions: A Story of Hope – Philippa Bridge-Cook 2,363
76. The Gardasil Experience in Denmark: One Family’s Story 2,345
77. What Do Fluoroquinolone Antibiotics Have in Common With Gardasil? – Lisa Bloomquist 2,338
78. Endocrine Disruptors and Your Son’s Penis Size – Chandler Marrs 2,324
79. Take A Health Survey 2,302
80. Endometriosis and Hysterectomy: Reality and Recovery – Angela Kawakami 2,300
81. Normal Thyroid Labs With Symptoms Of Hypothyroidism – Karl Johnson 2,285
82. Why Fatigue Matters in Thyroid Disease – Chandler Marrs 2,271
83. Pelvic Inflammatory Disease Post Endometriosis Surgery – Angela Kawakami 2,257
84. Thyroid Hormones, Mitochondrial Functioning and Hair Loss – Chandler Marrs 2,257
85. The Fluoroquinolone Antibiotic Side Effects Survey – Chandler Marrs 2,250
86. Thyroid Dysfunction with Medication or Vaccine Induced Demyelinating Diseases – Chandler Marrs 2,246
87. Endometriosis and Neuropathy – Chandler Marrs 2,219
88. Thyroid Hormones and Cardiovascular Function: New Research, New Neurons – Chandler Marrs 2,216
89. Hormones, Hysterectomy and the Hippocampus – Chandler Marrs 2,214
90. Fluoroquinolone Antibiotics Damage Mitochondria – FDA Does Little – Lisa Bloomquist 2,207
91. Hysterectomy and Brain Health – Chandler Marrs 2,203
92. Essure ® Sterilization Coils: The Good, The Bad, and The Ugly – Margaret Aranda 2,200
93. Heart Attacks in Women are Different: It Took Doctors Days to Diagnose Mine – Lisa Moffat-Hamilton 2,159
94. Low T – Evaluating the Risks of Testosterone Replacement – Jaime Heidel 2,147
95. Endometriosis and Transgender: Beyond Gendered Reproductive Health – Fox 2,126
96. Red Raspberry Leaf Tea to Relieve Menstrual Pain – Lisbeth Prifogle 2,120
97. From Lupron to Fibromyalgia, Hashimoto’s, Pericardial Effusion and More – Kerri 2,095
98. Physical Therapy for Endometriosis Adhesions and Symptoms – Leslie Wakefield 2,045
99. My Doctor is an Expert – Joan Lowe 2,035
100. Is Gardasil Mandated in your State – Lisbeth Prifogle 2,016

Crowdfund Hormones Matter – Buy an Unsubscription Now

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Hormones Matter is a labor of love, but an unfunded labor of love that needs your help. Hi, I am Chandler Marrs, PhD, founder, editor and chief trouble-maker at Hormones Matter. I want to continue our offerings and provide our community with as many resources as possible. This takes financial and human resources that I simply do not have. So I am offering you, our readers, community members, supporters, friends, family, and fellow health advocates, the opportunity to help crowdfund Hormones Matter.

Crowdfunding with a Twist – The Unsubscription

As with everything we do here at Hormones Matter, this crowdfunding campaign is a little bit different than others. Technically it’s not a crowdfunding campaign at all, because I am not going to offer you any kitschy certificates, t-shirts or other products you don’t need or want. Nope, I will not offer you any of the standard fair associated with traditional crowdfunding campaigns.

What I will offer is the continued health advocacy, science and medical reporting, and the research that you have come to trust, plus the much needed additions to the website that our community desperately needs. I will offer the opportunity to change healthcare dramatically, by giving voice to those with the invisible, difficult to diagnose and seemingly impossible to treat, diseases. And finally, I will offer the opportunity to contribute to a deeper understanding about medication safety and efficacy. If you believe in what we are doing here at Hormones Matter and want to be part of the healthcare solution, help us stay online and help me fund the next steps in our development.

Contribute Now by Purchasing a Hormones Matter Unsubscription

Yes, you read that correctly, an unsubscription. Why an unsubscription?  Well, I want our reporting, our research, everything we do, to be open to all. The unsubscription model, also called the pay-what-you-can model, allows those who can pay, to pay, and those who can’t afford to pay to still have access to all of the great health and science information we provide. I believe very strongly that one’s ability to access the latest health research should not be contingent on income, and hence, the unsubscription model.

If you have a few bucks and like what we do, send them over. If you have a few more and want to really see us grow, then buy a big unsubscription. If you’d prefer a one-time contribution, click the donate button.

Subscribe to an Unsubscription Now

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Donation in any Amount

Is this a Donation?

Well, yes and no. Hormones Matter was formerly an arm of a  B-Corp (for benefit corporation), that I ran for many years as a service to the community. Without the resources to run this type of business endeavor any longer, and in an effort to keep Hormones Matter alive, I have closed the corporation and moved Hormones Matter over to a single entity LLC. What this means is that any money you contribute is not tax deductible, for that I would have to be a not-for-profit enterprise. So while the donation is a contribution to our on-going operations, it is not a donation to a non-profit.  Your financial contribution will help keep Hormones Matter online.

On the Radio: Chandler Marrs and Leslie Botha Talk Hormones and Health

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Earlier this week, I had the great pleasure of speaking with Leslie Carol Botha on her radio show, Holy Hormones Honey, the Greatest Story Never Told, KRFC FM Fort Collins. We spent an hour discussing everything from pregnancy – postpartum mental health and the state of hormone research to women in clinical trials and vaccine safety.  We even talked politics, just a bit.

Front and center was the need for more research and data in all areas of women’s health and the Hormone’s MatterTM solution, a series of crowdsourced studies under the Real Women, Real DataTM, program. Currently, we have three studies underway with many more planned.

In the end, we decided, that we needed to found the Hormones MatterTM University or HMU. Seems like a good idea to me, what do you think?

I had a blast talking about women’s health and hormones and look forward to doing it again. If you want to know why I do, what I do or just want to learn a little bit more about me and why hormones matter in health, have a listen.

To listen to the interview: Do Hormones Matter in Women’s Health? Leslie Botha Interviews Dr. Chandler Marrs on Holy Hormones the Greatest Story Never Told.

To keep abreast of all the latest women’s health news, sign up for our weekly newsletter.

 

Why Hormones Matter

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I’ve been writing for Hormones Matter for several months now and I’ve been thinking a lot about just how much hormones really do matter. After all, we’re all only alive because of hormones when you get right down to it. Yet, most of us give very little thought to our hormones or why they matter until we’re forced to do so for some reason.

As young adolescents, we’re taught mostly in health class that hormones prompt our bodies to develop into those of men and women. We recognize that underarm and pubic hair growth is an indication that all is going well. Boys voices deepen and girls develop breasts. New sexual feelings slowly emerge and the world takes on new meaning and all things become more colorful. We become alive as it were and suddenly have another purpose – that of connecting sexually and of reproducing at some point. There’s a good amount of information about how hormones influence sex and reproduction. Sadly, the information seems to mostly end there. It wasn’t until my hormone-producing organs were removed through an unconsented hysterectomy and bilateral salpingo oophorectomy that I began to realize how much my hormones had mattered.

In simplest terms, hormones are chemical messengers which travel through our blood and enter cells, tissues and organs where they turn on switches to the genetic machinery that regulate everything from reproduction to emotions, overall health and well being. Certain hormones have an effect on particular cells known as ‘target cells’. A target cell reacts to a particular hormone because it bears receptors for that hormone. This is why there’s never a time in a woman’s life when she doesn’t need hormones. Hormones can be thought of as the life giving force that ‘animates’ us physically, mentally, emotionally and even spiritually. When a woman undergoes hysterectomy, hormone-producing organs are permanently removed and hormones are lost forever. It’s important to know that hormones aren’t only involved in the production of a new life (as in baby in the womb new life), they sustain all life.

Realizing How Much Hormones Matter

At the time of my father’s death from a massive heart attack in 2009, I was still reeling from hysterectomy and ovary removal in 2007. I’ll never forget the first time I saw my father’s body after he passed away. It hit me really hard to see him full of life one day and then see him completely and utterly lifeless the next. It hit my son Christopher even harder I think. I’ll never forget his comment as he looked at his grandfather’s ‘lifeless’ body just before the dreaded funeral. He said matter-of-fact like “Papaw’s spirit is gone. There’s no more animation.” Christopher’s observation was a very profound one indeed. In a very real sense, I suppose that is what death means – no more animation. I’d never thought of it exactly like that before.

Suddenly, I couldn’t help but think about how much I had changed since hysterectomy. It was as if the very life had been sucked right out of me too. I wasn’t dead, but I wasn’t really alive either – at least not in any way that mattered. Along with the loss of my female organs, I had lost my animation in many ways too. My eyes no longer sparkled. My skin no longer glowed. All things became dry, dull and lackluster. Everything became an effort and ‘feelings’ were no longer present. Remember how it felt when you became sexually aware? Well think of the opposite of that. While I once viewed the world in living color, things appeared mostly grey to me after hysterectomy and the loss of hormones. In short, I lost my animation.

Beyond reproduction and the other physiological functions ovarian hormones control, in many ways, these hormones animate us. They provide the subtle nuances that make life interesting – a life giving force that colors our physical, mental, emotional and even spiritual selves. To be animated is to have life, interest, spirit, motion and activity. What happens when a woman undergoes hysterectomy and castration? Pretty much the same thing that happens to a man who is castrated, she loses her animation, her color – everything that makes life interesting and worth living disappears. And this is on top of the health issues that arise from the loss of hormones.

There can be no question that hormones matter. It is too bad that we don’t know this until after they are gone. Please give this much thought before ever agreeing to removal of your hormone-producing and life-sustaining organs. Always weigh the benefits and risks.

Hysterectomy Research

Hormones Matter is conducting research on hysterectomy outcomes. If you have had a hysterectomy, please take a few minutes to complete The Hysterectomy Survey.

What is DES and Why You Should Care

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Diethylstilbestrol or DES is synthetic estrogen developed in the late 1930s. It was initially approved by the FDA in 1941 for vaginitis and as an early hormone replacement therapy for menopausal women.  It was later approved a variety of low estrogen indications. In 1947, the FDA approved its use in pregnant women with a history of miscarriage. DES had been used off-label for miscarriage prevention since the early 1940s, despite the fact that little evidence supported its use and animal studies indicated clear carcinogenic and congenital reproductive abnormalities in the offspring.

After 10 years of widespread use and marketing, a double-blind, placebo-controlled study on the efficacy of DES was finally conducted. As one might expect, it was found ineffective in preventing miscarriage. In fact, women on DES had a higher risk of miscarriage. Later studies in the 1960s began detailing the adverse events associated with this drug. Despite mounting evidence of the dangers of diethylstilbestrol, it remained on the market and widely used through the early 1970s in the US and into the 1980s in some European countries.  In the US alone, it is estimated that between 5-10 million women and their children were exposed to DES.  Because the compound was never patented, 287 drug companies sold DES under a multitude of brands  and for an array of low-estrogen conditions.

In addition to diethylstilbestrol use in humans, it was used widely in farm animals to fatten up the chickens and cattle, beginning in the early 1950s and through the 1970s. DES was found to cause cancer and interestingly enough, cause gynecomastia (man boobs) and sterility in the poultry workers. Well before DES was banned in humans, the FDA banned it in poultry under the newly enacted Delaney Clause to the FDA 1958.  It seems man boobs and sterility was all it took to ban the product in chicken farms.  Miscarriage, congenital abnormalities and cross-generation cancer risks, on the other hand, were not sufficient to initiate its ban in large cattle or humans. It was another 20 years before diethylstilbestrol was banned in cattle or humans and many years after before it was removed from the food chain (if it even is now).  “In 1980, half a million cattle from one hundred and fifty-six feedlots in eighteen states were found with illegal DES implants.”  Even upon FDA’s decision to withdraw its approval of DES in cattle and feed, it did so on grounds of the procedural non-compliance of the manufacturers, erstwhile maintaining the safety of diethylstilbestrol, “because there is no evidence of a public health hazard.”  Despite its clear carcinogenic and teratogenic risks, it is still used in veterinary care.

Diethylstilbestrol Risk for Humans

Amongst those suffering the most from DES exposure are men and women who were exposed in utero as developing fetuses.  DES was given to pregnant women from the 1940 through 1971 in the US and into the 1980s in some European countries. If you were born anytime between 1940 and 1980, ask your mom if she was given DES to prevent miscarriage. It was sold under dozens of brand names (click here for brand names).

Sons and Daughters of DES

The range of depth of reproductive abnormalities, endocrine and health issues found in the children and grandchildren of DES moms, is expanding regularly. If your mom or grandmother was given DES, here is a list of health issues to look for:

DES Daughters

In a large cohort study comparing the reproductive health of the daughters of women prescribed DES during pregnancy to the health of women whose mothers had not been given DES, researchers found a 2-8 times higher incidence of the following conditions:

  • Infertility
  • Spontaneous abortion
  • Ectopic pregnancy
  • Second trimester pregnancy loss,
  • Preterm delivery
  • Preeclampsia
  • Stillbirth
  • Neonatal death
  • Early menopause
  • Breast cancer
  • Cervical neoplasia
  • Clear cell adenocarcinoma

The increased risk of miscarriage and adverse pregnancy outcome in DES daughters is overwhelmingly linked to structural abnormalities with uterus. Fully 69% of DES daughters who have had difficult with infertility and miscarriage have an abnormally shaped uterine cavity or structural changes to the cervix (44%).

DES and Endometriosis

Of particular interest to Hormones Matter followers, DES exposure in utero is linked to an 80% increase in endometriosis. We will be digging deeper into the DES – endometriosis connection in the coming weeks.

DES Sons

Sons of women given DES during pregnancy are three times more likely to have structural abnormalities of the genitals including:

  • epididymal cysts
  • undescended testes
  • extremely small testes
  • hypospadias (misplaced urethral opening)
  • micropenis (some, but not all)
  • increased risk of infertility
  • increased risk of testicular and prostate cancer (although the research has just begun)

In the animal research, offspring of DES exposed mothers shows a vast array of structural and morphological changes across multiple physiological systems ranging from sex reversal in male fish to structural and functional changes in pancreatic cells. The full scope of damage from DES is yet to be determined.

DES Grandchildren

Yes, there are third generation effects from this drug. Researchers are just beginning to untangle the third generation effects. In women, menstrual irregularities appear more common as do the various forms of cancer, but the data are unclear. In men, hypospodias may be more frequent, but again the data are mixed.

Endocrine disruptors like diethylstilbestrol impact human health in ways we are only just beginning to understand. The current methods for measuring and calculating risk for endocrine disruptors is out-dated and based on standard, linear, dose-response curves that not only fail to account for how hormone systems work, but also fail to address possible transgenerational effects. Hormones matter and sooner or later we must address the broader endocrine system in pharmaceutical and environmental regulation. As women, we ought to be fighting for sooner.

Why Hormones Matter to Me

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The Problem

A few days ago, I received a text from my older sister, Megan. “Becca [our younger sister] is in the hospital. She started bleeding so heavy she couldn’t leave the bathroom and has cramps so bad she was puking. She was at band and they called an ambulance! I’ll keep you posted.”

My first thought was, oh my god, how embarrassing. My second thought, oh my god, not Becca too. As I’ve written about before, my periods are less than normal. Oh how I envy those women who menstruate like clockwork. Those who can plan weddings, vacations, military exercises, etc. around their cycle without worrying that their bodies will evoke a surprise visit from that miserable old hag, Aunt Flow. As I have also written, I cannot take birth control to regulate my hormones. The various times I have tried, like Becca, I ended up in the ER from extreme heavy flow.

The Consistent Answer – Birth Control

Becca is eighteen years old and not sexually active and has never had a need to be on birth control. Between our mother, who had the same reactions that I did years ago, and my horror stories, I doubt she will ever be tempted to try. Still, I said to Megan and Mom prior to her doctors appointment, “They are going to try to force her to take birth control.” I know because that is the ONLY option I have ever been given. More than once I have had medical professionals glare at me and respond, “Well if you don’t want to take birth control there is nothing I can do for you.”

Becca went to her first gynecologist appointment today (congrats Becca you are a woman now!). Sure enough, Megan called me furious saying, “All they are willing to do is give her more pain killers and prescribe her birth control.”

I responded, “Not that I want to say I told you so, but I told you so. I knew that’s all they would do without any other tests ruling anything more serious out. Ugh, I freaking knew it!”

Side note: We are Irish, German, Scottish (and my Dad swears we’re of Viking descent on his side) and on top of that our hormonal imbalances; needless to say, anger management is not one the Prifogle Women’s strong points.

Becca explained my experiences with birth control to the doctor and expressed that she didn’t want to do that, but the doctor told her and Mom that it was her only option. They scheduled an ultrasound to rule out ovarian cysts, but in all likelihood it will just be something poor Becca has to live with as well.

A multivitamin that has maca root, chaste tree berry and red raspberry leaf tea, as well as acupuncture, have help me, but we’ll see what Becca and Mom decide to do.

Why Hormones Matter and Why I Write

When I started writing for Lucine’s online magazine, Hormone’s Matter, Chandler Marrs told me the statistic that <30% of clinical practice guidelines in OB/Gyn are evidence based. I was in shock, but then I thought of all my horrible experiences with my periods and doctors lack of willingness to do anything about it outside of synthetic hormones (and for some women this is great – I just don’t happen to be in that category of women). As busy and exhausted as I am (and aren’t we all) I continue to research, write and help build this online community because that statistic is ridiculous. Hormonal birth control cannot be the band-aid, cure-all for women’s health any longer! We have to start figuring out what the problem is and dealing with the cause, not the symptoms? It could be as simple as eliminating endocrine disruptors and hormones from our diet/lifestyle or adding exercise, or it might be something more complicated and un- or misdiagnosed. For Becca’s sake, I hope it’s something as simple as a diet change.This isn’t just a female problem either. As John-Brandon Pierre wrote in Why Men Should Care About Women’s Health:

“It is our duty as men to help care for and help provide security for our women. To help strengthen them so that they can live out their lives in the most meaningful way they choose. To support them and help them find answers to the problems that plagues them. In doing so we enrich our future and we do our part to better understand what we cherish the most – our women.”

Thank you for your support and please continue to spread the word about Lucine Biotech and that HORMONES MATTER!