ocella Archives - Hormones Matter

Pill Bleeds Are Not Periods

Published on June 3, 2015

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The Pill is not just contraception anymore. It has become standard treatment for everything from acne to endometriosis to irregular periods. Yes, hormonal birth control can mask symptoms, but it cannot “regulate” hormones or periods in any meaningful way.

Hormonal birth control does not augment or regulate hormones. Instead, it suppresses ovarian function and shuts down hormones completely. It replaces endogenous hormones with synthetic steroids, and that’s not good enough for women’s health. Real hormones have many benefits for health that synthetic steroids simply cannot deliver.

Real Hormones versus Synthetic Hormones

Our real endogenous hormones are estradiol and progesterone. In contrast, synthetic steroids are ethinylestradiol, levonorgestrel, drospirenone, and many others. Real hormones and synthetic steroids are similar molecules, but they’re not identical and as a consequence, synthetic steroid have many different effects on the body, some of which we are only now beginning to understand.

For example, estradiol improves insulin sensitivity. Its synthetic counterpart ethinylestradiol impairs insulin sensitivity [1] (which is one of the ways the Pill causes weight gain). Progesterone is beneficial for hair, brain health, and bone density, but its synthetic analogues levonorgestrel, drospirenone, and medroxyprogesterone have quite different effects. They cause hair loss, depression [2], and reduced bone density. Moreover, the drospirenone progestin found in the Yaz, Yasmin and Ocella series of birth control pills, increases the risk of heart attack and stroke six fold. Its modified shape blocks what are called the mineralocorticoid receptors. These receptors are responsible for salt and water balance (think swelling) and blood pressure.

The only way that ethinylestradiol and progestins are similar to real hormones is that they induce a uterine bleed. They can even induce it monthly, but only if they’re dispensed that way.

Why Bleed?

Who really cares about a bleed for its own sake? If women can’t have real hormones, then why have a monthly bleed at all? It is merely to give the appearance of a period, and reassure women that they’ve had a period (when they haven’t). A bleed does prevent excess build-up of the uterine lining, but it does not have to be monthly. It can be quarterly or yearly or any time we withdraw from the synthetic steroids. Regardless of when we choose to bleed, the pill bleed is not the same as menstruation. Remember, the purpose of oral contraceptives is to block ovulation and prevent pregnancy. Without ovulation, our bodies do not produce endogenous hormones. Indeed, as any woman who has gone off of the pill after a long period of usage will tell you, it takes some time for ovulation and hormone production to begin again.

Normalizing our Periods: A Myth

Interestingly, the “regulation” of periods was the Pill’s earliest cover story. When the Pill was first developed, it could not be sold as contraception because contraception was not legal. Instead, the Pill was ostensibly prescribed to “normalize” periods. “Normalize” was a quaint euphemism which really just meant to be “not pregnant” (wink-wink).

Five decades later, and the Pill’s early cover story has now taken hold as a kind of weird counterfeit reality. Doctors readily prescribe oral contraceptives for all manner of female reproductive disorders, the most common of which is to ‘normalize’ the menstrual cycle. What they, and most women, fail to realize is that the monthly bleed precipitated by the withdrawal of synthetic steroids, is not a real period. It is simply a withdrawal bleed.

It’s time to end it. It’s time to bring back real periods.

There Is Another Way

As a naturopathic doctor working in women’s health for twenty years, I want my patients to have real periods. More precisely, I want them to have a follicular phase and make estradiol. I want them to ovulate, so they can then have a luteal phase and make progesterone. In short, I want my patients to make real hormones and to enjoy their many benefits.

There’s another reason I want my patients to have real periods. A healthy, regular period tells me that all is well with her underlying health. If a woman does not have healthy periods, then I keep working with her until she does. We use her period as a helpful, useful marker guiding her health decisions. We think of it as her monthly report card.

It’s not always easy to restore healthy periods, but it can be done. But with a little perseverance, natural treatments such as diet, supplement and herbs work well, and they give women what they deserve: A real period rather than a pharmaceutically induced bleed.

Real Risk Study: Birth Control and Blood Clots

Lucine Health Sciences and Hormones Matter are conducting research to investigate the relationship between hormonal birth control and blood clots. If you or a loved one have suffered from a blood clot while using hormonal birth control, please consider participating. We are also looking for participants who have been using hormonal birth control for at least one year and have NOT had a blood clot, as well as women who have NEVER used hormonal birth control. For more information or to participate, click here.

References

Kojima T et al. Insulin sensitivity is decreased in normal women by doses of ethinyl estradiol used in oral contraceptives. Am J Obstet Gynecol. 1993 Dec;169(6):1540-4. PMID: 8267059
Kulkarni J et al. Depression associated with combined oral contraceptives–a pilot study. Aust Fam Physician. 2005 Nov;34(11):990. PMID: 16299641

High Blood Pressure in Women: Could Progesterone be to Blame?

by Chandler Marrs, PhD

Published on August 25, 2014

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High blood pressure develops for a number of reasons, with poor diet, lack of exercise and medication key contributors to chronic hypertension. Explaining high blood pressure in young, otherwise active, athletic and healthy individuals is difficult at best, but when the blood pressure seems to wax and wane for no obvious reason, diagnosing and treating this form of hypertension can be downright impossible.

This is where an good percentage of the female population find themselves; with treatment refractory high blood pressure, that worsens across the menstrual cycle, during pregnancy and in response to certain formulations of oral contraceptives. Unbeknownst to many of these women and their doctors, they are carriers of a genetic mutation that raises their blood pressure relative to circulating progesterone concentrations. For these women, when progesterone concentrations are high, as during the luteal phase of menstrual cycle, and especially during pregnancy, blood pressure skyrockets uncontrollably. When progesterone concentrations are low and provided lifestyle variables are in check, blood pressure is more manageable.

Mineralocorticoids and Blood Pressure

Blood pressure is controlled in large part by what is called the mineralocorticoid system. This is a set of both steroid and peptide hormones that interact with the vasculature and the kidneys to increase or decrease blood flow. The mineralocorticoid hormone receptors are at the center of this system. Binding to these receptors is the mineralocorticoid hormone called aldosterone. Aldosterone regulates salt homeostasis and whether the kidneys store salt and water or release it.

Sensors within the kidneys monitor sodium concentrations. When there is not enough salt, they release the peptide hormones renin and then angiotensin I and II. The renin-angiotensin system then activates the release of the steroid hormone aldosterone. Aldosterone binds to the mineralocorticoid receptors and signals the kidney to reabsorb more salt. More water is also reabsorbed, and with those changes, plasma volume increases. Increased plasma volume, increases vascular volume which in turn requires a higher cardiac output. Increased cardiac output then leads increased blood pressure. The reverse is also true, decrease salt reabsorption and we get hypotension or low blood pressure.

Regulating Blood Pressure

At every junction there can be errors or mutations in this system and compensatory reactions to environmental or dietary changes. Add those possibilities to the variety of other factors that control blood pressure (baroreceptors, natriutetic peptides, kinin-kallikrein, adrenergic receptors, nitric oxide and endothelin) and it is easy to see why hypertension is sometimes difficult to manage. Women, however, have the added bonus of constantly changing hormone concentrations, across the menstrual cycle, pharmaceutically, across pregnancy and across menopause. Since the mineralocorticoid receptors, like all steroid hormone receptors, bind promiscuously to a bunch of different hormones, it is easy to see how drastically changing hormone concentrations can impact salt and water homeostasis (premenstrual swelling, pregnancy swelling, oral contraceptive swelling), and ultimately, blood pressure. Add a little stress to this mix and we have a recipe for hypertension. Indeed, it should be noted that both cortisol, the stress hormone, and progesterone, bind more strongly to the mineralocorticoid receptor than aldosterone.

Progesterone Binds to Mineralocorticoid Receptors

Progesterone, the reproductive hormone that prepares the endometrium for implantation during the luteal phase of the menstrual cycle and supports the pregnancy once underway, binds to mineralocorticoid receptor. The relationship between progesterone and blood pressure is complex, but mostly progesterone blocks the mineralocorticoid receptors and lowers blood pressure. In some women, however, the shape of the mineralocorticoid receptor is altered, allowing for increased progesterone binding in such a way that it activates the signals sent from the receptor. So rather than block the mineralocorticoid-aldosterone pathway, it launches it. Progesterone then becomes the conduit for increasing salt and water retention and increasing blood pressure.

Progesterone and High Blood Pressure

For women who carry this gain-of-function mineralocorticoid receptor mutation, high blood pressure emerges early, before the age of 20 and, for all intents and purposes, is refractory to the normal lifestyle changes and many medications that reduce blood pressure, except perhaps diuretics. The high blood pressure often becomes severe during pregnancy. It may also become severe with any drug that increases progesterone or decreases aldosterone including with oral contraceptives, synthetic progestins (medroxyprogesterone, micronized progesterone, prempro and related), and blood pressure medications that block aldosterone (spironolactone) and are derived from 17a- spirolactone. Fourth generation progestin, contraceptives or hormone replacement therapies (HRT) containing drospirenone are particularly dangerous, as they both bind to progesterone receptors strongly and block mineralocortiocoid activity simultaneously.

It should be noted that boys and men also carry this mutation and are susceptible to early onset hypertension.

The Problem with Progesterone Mediated Blood Pressure

The problem with progesterone mediated high blood pressure is one of recognition. High blood pressure in general is not recognized in young women. Blood pressure mediated by progesterone concentrations, whether via endogenous and menstrually-related changes or the use of synthetic progestins, is all but completely unrecognized. Genetic testing in this population is unheard of. Consequently, many young women are at risk for cardiac and thromboembolic events and do not know it. Could the sudden deaths reported in association with drosperinone oral contraceptives be related to unrecognized gain of function mineralocorticoid mutations? Possibly.

During pregnancy, the risk is magnified exponentially as progesterone concentrations increase several hundred fold. Hypertension accounts for 6% of all pregnancy complications, one wonders what percentage are related to progesterone? No one knows, because it is not studied.

For older women, though blood pressure is routinely monitored, connections between synthetic progestins in HRT and blood pressure elevations may only be cursorily understood, leaving many women open to inadvertently increasing their risk for heart attack and stroke coincident with attempts to manage menopausal symptoms. Although, hormones naturally decline during menopause, the re-supplementation of progesterone and progestins can be problematic for these women.

Fourth Generation Progestins: The Dangers of Drospirenone

For women with the gain of function mutation, certain forms of oral contraceptives and HRT can be deadly. The 4^th generation progestins contained the Yas, Yasmin, Ocella series of birth control pills and in the Angeliq brand of HRT, are derived from a synthetic progestin that blocks the mineralocorticoid receptor directly.

Drospirenone is a progestin and mineralocorticoid antagonist derived from 17a- spirolactone. 17a- spirolactone blocks aldosterone. Under normal circumstances, blocking aldosterone’s ability to bind with mineralocorticoid receptors might be a good thing and reduce high blood pressure, particularly in folks who have aldosterone based hypertension or who are in heart failure. In other populations, however, blocking aldosterone might not be such a great idea.

Drospirenone based oral contraceptives and HRT formulations contain progestins that bind with equal affinity to the progesterone receptor compared to endogenous progesterone, but bind 500X more strongly to the mineralocorticoid receptors than aldosterone. This is problematic for most women, even if they don’t carry the gain-of-function mutation. Drospirenone based contraceptives increase the rate of serious cardiovascular events by as much as 6X compared to the older contraceptives. In women who carry the gain of function mineralocorticoid receptor mutation, taking a drosperinone based oral contraceptive or menopausal replacement therapy, the results can be deadly.

Drospirenone – Mineralocorticoid Receptor Connection

If one has the gain of function mutation, where the mineralocorticoid receptors preferentially bind with progesterone and its metabolites, blocking what remaining aldosterone controlled feedback loops of salt/water balance, skews the receptor activity in such a way that it is always on, and always telling the kidneys to reabsorb more salt and water. Similarly, increasing progesterone concentrations unnaturally, with drosperinone, or any other progestin, quantitatively increases binding with the mineralocorticoid receptors, displacing aldosterone, removing important feedback controls and creating a state of perpetual progestin-mineralocorticoid activation.

Epigenetic Factors in Blood Pressure

Environmental toxicants and pharmaceuticals induce what are called epigenetic changes in protein expression. Epigenetic means beyond genetics. These types of changes don’t alter DNA per se, just alter whether a certain protein codes are activated or deactivated. There are number technical mechanisms by which epigenetic variables can alter receptor expression and function. For other receptors, especially the glucocorticoid and estrogen receptors, many of these epigenetic mechanisms have been elucidated. Not so for the mineralocorticoid receptors. Certainly, with environmental exposures, which are all endocrine disrupting in some manner or another, it is possible to create constitutively open mineralocorticoid receptors, much like the gain of function mutations. This would mean that millions of women could be a great risk when using drospirenone based oral contraceptives or HRT, progesterone increasing or mimicing drugs (most oral contraceptives and HRT), aldosterone blocking agents from spirolactone and during pregnancy. Even across the menstrual cycle, blood pressure would be expected to wax and wane relative to circulating progesterone concentrations.

Final Thoughts

Maybe it is time to move beyond the one hormone, one receptor, one function view of endocrinology. It’s certainly time to address the role of cycling hormones on human physiology. Cycling progesterone concentrations impact blood pressure; recognizing this simple fact would help women and their physicians develop more reasonable and effective approaches to managing high blood pressure.

Will the Sunshine Act Curb Pharma Payments to Doctors?

by Chandler Marrs, PhD

Published on February 12, 2013

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Just two weeks ago, as part of the Affordable Care Act, the Centers for Medicare and Medicade Services published its final rule on the reporting mandates for physician payments from pharmaceutical and medical device makers. Called the Physician Payment Sunshine Act, this law requires:

applicable manufacturers of drugs, devices, biologicals, or medical supplies covered by Medicare, Medicaid or the Children’s Health Insurance Program (CHIP) to report annually to the Secretary certain payments or transfers of value provided to physicians or teaching hospitals (“covered recipients”).

Why Is This Important?

For too many physicians, the medications they choose to prescribe are influenced by these payments. A case control study at a university hospital found that physicians who requested a new drug be added to the formalary were 19X more likely to have received money or gifts from the drug company. According to the New England Journal of Medicine as of 2007 fully 94% of all physicians accepted gifts from pharma, although by 2009, only 84% of physicians accepted gifts from pharma.

In their Dollars for Docs series, Propublica not only detailed the trail of money from the pharmaceutical industry to physicians and the changes in prescribing practices that ensued, but also, found that over 250 of the physicians receiving these payments had been disciplined by their state’s medical boards with the public never the wiser.

Wouldn’t you want to know if your physician was receiving payments to ‘consult’ on a particular drug or medical device? What if that drug or device turned out to be dangerous like, Avandia or Vioxx or in the case of women’s health Yasmin, Yaz or Ocella or even the vaginal mesh implants? I would. And soon, you will be able to find this information, at least for those physicians that accept medicare or medicade. For the remaining physicians, we’ll have to rely on the stellar, investigative reporting of organizations like Propublica.

What Is the Physician Payment Sunshine Act?

The Physician Payment Sunshine Act mandates payments or ‘transfer of value’ to physicians be reported to the Secretary of Health and Human Services. Collection of this information is set to begin in August with full compliance and reporting expected in 2014.

The cool thing about this act, if it is implemented correctly, is that payment or transfer of value includes money for marketing activities, such as promotional or conference talks and consultation services. It also will include research grants and “charitable” contributions (which usually come with some promotional strings attached), funding to attend conferences, honoraria and royalties and license fees. The pharmaceutical and device companies making these payments will be required to list names, address, amount of payment, date of payment(s) and describe the service for the payment made for anything over $10. The database will be searchable so that patients can determine what monies their physicians received from pharma or device companies.

Where the Sunshine Act Fails

From the original to the final regulations, a work-around for paying physicians to speak at pharma sponsored continuing medical education (CME) events was added. According to the regulations, so long as the sponsoring company doesn’t pay the physician/speaker directly, those fees are acceptable and need not be listed publicly. Instead, the pharma company must pay a third party vendor to arrange and pay the speakers. CME conferences are where most physicians learn the latest drug therapy, device or medical technique. It is unlikely that speakers at these conferences will speak against the sponsor’s product. Funneling the payments through a third party vendor, who is also paid by the sponsor, is no more than a quick pass at laundering the fees.

What Do Physicians Think About the Sunshine Act?

The opinions are mixed, at least publicly. Some physicians are fully behind the new efforts in transparency and have begun their own campaigns to disentangle the marketing relationships between pharma and physicians. The National Physicians Alliance sponsors the Unbranded Doctor campaign:

The National Physicians Alliance’s Unbranded Doctor is unmasking the pharmaceutical industry’s bogus claim that its marketing efforts are just educational ventures for physicians. By signing up physicians to renounce gifts, lecture fees, and “education” from companies, the Alliance is championing objectivity, integrity, and professionalism.

—Jerome Kassirer, MD
former Editor-in-Chief, New England Journal of Medicine

Similarly, the British Medical Journal (BMJ) has positioned itself as a lead proponent of transparency and open data. On the other hand, CME released a survey of over 500 physicians asking if the new regulations to list publicly whether industry sponsored their attendance at CMEs would curtail their attendance. The result was a resounding – yes.

75% of physicians said the disclosure rules would affect their decision to attend at least somewhat.
47% of physicians said the disclosure rules would affect their decision to attend to a great extent.
46% of CME speakers said the disclosure rule would affect their decision to participate as a panelist or presenter to a great extent
25% percent said it would somewhat affect their participation

Will the Sunshine Act Curb Pharma Payments to Doctors?

Probably not. Unless and until full transparency about medical research, clinical trials and adverse events are made open and accessible to patients and physicians, medical marketing, fabricated data or omitted data, publication bias, and conflicts of interest will continue to pervade our healthcare system. Dangerous medications like the Yasmin suite of birth control pills and unsafe medical devices like J&J’s Gynecare Prolift will remain on the marketplace long after any reasonable person could vouch for their safety.

The Sunshine Act will, however, give patients one more tool to evaluate their physicians and give researchers, investigators and others a way to identify and publicize bad behavior. Who knows, maybe it will even save some money.

To find out if your physician receives money from the pharmaceutical industry go to Dollars for Docs.

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