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Let’s Talk About Sex, Baby: Hormonal Contraception & Libido

Published on April 4, 2024

9334 views

“If sexuality is one dimension of our ability to live passionately in the world then in cutting off our sexual feelings we diminish our overall power to feel, know, and value deeply.” –Judith Plaskow

This quote raises an interesting question. If owning our sexuality gives us power, then who benefits from limiting that power? And why is limiting that power an acceptable side effect of hormonal contraception?

During the Nelson Pill Hearings, Dr. M. James Whitelaw testified (page 6015): “How many adult males would be willing to take an oral contraceptive faithfully if they were told that instead of a possible 50-plus adverse side reactions only one remained, that being the possible loss of sex drive and libido? [Laughter]”

What is the implication here? Women can be denied their full sexual capability but the idea of men suffering the same is laughable? Holly Grigg-Spall speaks to that in her book Sweetening the Pill (page 50):

“The pill’s impact on the libido has been publicized but it is generally dismissed with humor. The libido is seen as distinct from women’s emotional and physical health, whereas with men it is linked. The female sex drive is not celebrated or seen as essential to her femininity or sexuality… Research that indicates that lowered libido is experienced by a large number of women on the pill is undercut by the cultural assumption that most women have little real interest in sex regardless of this drug.”

Sexy But Not Sexual

And she’s right. Women are constantly told to be sexy but not sexual. It would seem that hormonal birth control would provide exactly that type of woman. One who could have sex without the consequence of getting pregnant, therefore highly desirable to men; but one who could not fully embrace the power of her own sexuality due to a medication-induced lack of libido. Is this really what we want? A society of women that are physically available for sex but completely disconnected from the powers of her own sexuality? Again I will ask, who benefits from keeping women in that robot-like state?

“The quality of a woman’s sex life, unlike that of a man’s, does not seem to concern the drug companies or the (male) research establishment… Women who reported changes in their sex drive often heard that old refrain: ‘It’s all in your head.’ But the male sex drive is considered so important by the drug companies that it is always studied in conjunction with new male contraceptives, just as it is almost always mentioned in arguments against the condom.” –Barbara Seamen in The Doctors’ Case Against the Pill

It’s true. We hear the argument that condoms lessen sensation during sex. But for whom? Men. Yet for women who use hormonal birth control, low libido and loss of sensation during sex are some of the least dangerous side effects they can expect. Heather Corinna put it so well in her article “Love the Glove” that even Grigg-Spall quoted her:

“If we’re going to talk about condoms changing how sex feels, we need to remember that something like the pill does too, and, unlike condoms, it changes how a woman feels all the time, both during and outside of sex… Other methods of contraception can cause pain and cramping, unpredictable bleeding, urinary tract infections, depression and a whole host of unpleasant side effects. Condoms are the LEAST intrusive and demanding of all methods of contraception, even though some guys talk about them — without considering this perspective — like they’re the most. If guys could feel what life can be like on the pill, use a cervical barrier or get a Depo shot, they’d easily see condoms for the cakewalk they are.”

It’s not just the pill that is damaging to women. As Grigg-Spall explains, Depo Provera (“the shot”) is specifically used to decrease sex drive in sex offender rehabilitation programs. There is something seriously wrong when a birth control option offered to women is the exact same medication used as pharmaceutical castration for sex offenders.

FSD – Female Sexual Dysfunction or Female Sexuality Discouraged?

According to a study of female German medical students published today in The Journal of Sexual Medicine, women taking non-oral and oral hormonal contraceptives were at highest risk of Female Sexual Dysfunction (FSD). Interestingly, women using non-hormonal contraceptives were at lowest risk for FSD, more than women not using any contraceptive.

“Sexual problems can have a negative impact on both quality of life and emotional well-being, regardless of age,” said researcher Dr. Lisa-Maria Wallwiener of the University of Heidelberg, Germany. “FSD is a very common disorder, with an estimated prevalence of about two in five women having at least one sexual dysfunction, and the most common complaint appearing to be low desire.”

Side Effects – Affecting More Than Just the Patient

Why is this okay? Why do we accept this? If a woman is experiencing sexual dysfunction, it not only affects her but it affects her partner as well.

Dr. Philip Ball testified about this very problem at the Nelson Pill Hearings back in 1970 (page 6493): These unhappily newly married women do not know if it is the wrong man, the wrong town, the wrong job, the wrong year, the wrong apartment, or yet something else, when it is really many times the wrong pill.

And he’s not incorrect. Research now shows that taking birth control pills affects women’s taste in men. According to this article from the Scientific American, women on the pill seem to prefer men who are genetically similar to themselves.

“Women who start or stop taking the pill, then, may be in for some relationship problems. A study published last year in Psychological Science found that women paired with MHC-similar men are less sexually satisfied and more likely to cheat on their partners than women paired with MHC-dissimilar men. So a woman on the pill, for example, might be more likely to start dating a MHC-similar man, but he could ultimately leave her less sexually satisfied. Then if she goes off the pill during the relationship, the accompanying hormonal changes will draw her even more strongly toward more MHC-dissimilar men. These immune genes may have a “powerful effect in terms of how well relationships are cemented,” says University of Liverpool psychologist Craig Roberts, co-author of the August paper.”

How any of this is connected to relationship issues, divorce rate, infertility, one can only speculate. But it’s clear that the sexual side effects caused by hormonal contraception are no laughing matter.

Sex is a big part of life. The ability to connect with each other and derive great pleasure from sex is not just a perk of being a human. It is our birthright. And to deny that birthright is to limit our power as women. That’s not what I consider an “acceptable side effect.”

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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This article was published originally on July 14, 2016.

How Hormones Rise and Fall Throughout the Menstrual Cycle

by Brandy Searcy

Published on October 31, 2023

5182 views

Fertility Awareness Method For Contraception

Back in 2012, I was really sick and while we were trying to figure out what was going on, my doctor recommended I discontinue hormonal birth control for a while. For about 6 months, I used conductivity monitoring to avoid pregnancy. Each morning, I’d record the conductivity of my salivary and vaginal secretions looking for a change to indicate I was approaching ovulation and another change to indicate ovulation had occurred.

Back then, it felt confusing to me and a little black box”ish”, so when I was cleared to go back on hormonal birth control, I went back on it and didn’t give another thought to Fertility Awareness Methods (FAMs), until I decided to ditch hormonal birth control again.

This time, I did a deep dive and discovered new methods alongside familiar methods of FAM, and I went head-over-heels into the science of it.

In the decade since I relied on FAMs last, at-home urinary monitors are now available, and being a data driven girl, this is the method I opted for. Qualitative devices such as the ClearBlue Fertility Monitor (CBFM) didn’t quite offer the numbers I craved, so I went with the Mira Fertility Monitor even though, to date, no FAM endorses the use of this monitor for contraception (though Marquette University is actively testing the Mira against the CBFM with its protocols).

This ability to monitor your hormones at home also revolutionizes maintaining healthy hormonal balance and body literacy. Indeed, body literacy and the natural rise and fall of hormones throughout a healthy cycle is the topic of this post.

Hormones of the Menstrual Cycle

In this article, we will discuss:

follicular phase and ovulation
- follicular development, how follicles are recruited and begin maturing throughout a woman’s reproductive life span
- how testosterone and estradiol are produced in the developing follicles
- the role of the hypothalamus and pituitary glands in follicular development and ovulation
- the role of progesterone in ovulation
luteal phase
- key changes in hormone production during the luteal phase (second half of the cycle)
finally, the entire menstrual cycle will be summarized in a single graph showing the rise and fall of hormones throughout the cycle

Why does all of this matter? When you understand how the menstrual cycle works, it becomes much easier to determine hormonal imbalances and much easier to navigate fertility. Women are only fertile for around a maximum of 5 days during any given menstrual cycle and when you have a condition like PCOS (polycystic ovarian syndrome) or experience delayed ovulation (or anovulation) for any reason during a cycle, menstrual cycle literacy makes it possible to pinpoint your fertile days when trying to conceive and naturally improve your chances of conception in each cycle.

For women who are not trying to conceive, cycle awareness is profoundly beneficial to overall health because you are better able to determine which part of your cycle is unhealthy and better able to address the underlying imbalance simply by knowing how your cycle works. Maintaining a healthy cycle throughout your reproductive years is of utmost importance even when your intention is to avoid pregnancy because the reproductive hormones impact every system within your body and are critical for everything from maintaining a healthy weight to a healthy heart.

This particular article (while containing lots of information) is an overview of the topics bulleted above. You will find a more in-depth discussion of these topics in this post.

An Overview of Follicular Development

Non-cyclical follicular development: Early follicular development of pre-antral follicles (follicles that don’t respond to follicular stimulating hormone) happens in a way that is not well understood by modern science and this part of follicular development is not governed by the menstrual cycle but instead occurs throughout a woman’s reproductive years beginning at the onset of puberty and ending with menopause.

Cyclical follicular development: A follicle is a structure within the ovary and it contains an ovum (immature egg). Each ovary houses several hundred thousand follicles at birth and throughout a woman’s reproductive life, these follicles mature and are responsible for releasing the reproductive hormones, estradiol and progesterone, which control release of these hormones:

GnRH (gonadotropin releasing hormone) released by the hypothalamus in a pulsed pattern
FSH (follicular stimulating hormone) released by the pituitary gland
LH (luteinizing hormone) released by the pituitary gland

The brain’s role in follicular development and ovulation: The tempo at which GnRH releases from the hypothalamus controls the secretions of FSH and LH by the pituitary, and these two hormones influence ovarian hormone patterns and those ovarian hormones affect the tempo of GnRH pulses by the hypothalamus. This feedback loop is what the term, hypothalamic-pituitary-ovary (HPO) axis refers to. It is important to know about the brain’s involvement in follicular development and ovulation because when there is a problem with the menstrual cycle, practitioners generally look at where in this axis the misfire is occurring. Conditions like hypothalamic amenorrhea (HA) arise due to an issue with the release of GnRH from the hypothalamus and we will revisit this condition along with others caused by a dysregulation of hormonal release in the brain rather than the ovaries in future articles.

Selection of one follicle for ovulation: Once follicles have matured into antral follicles, further development is governed by FSH and the follicles need FSH to not only continue growing but also to prevent atresia (follicular death). More than one follicle matures during each menstrual cycle and because of the well-designed negative feedback between estradiol concentrations and FSH, the fastest growing follicle generally outcompetes all other follicles by releasing more estradiol, which then suppresses FSH production and starves out the remaining developing follicles. The dominant follicle survives this period of FSH famine because it has more FSH receptors. The additional FSH receptors make it better able to sequester the small amounts of FSH released at this time. It is also larger and has more energy reserves than smaller and slower growing follicles. This is why women typically release only one egg (mature ovum) at ovulation.

Testosterone and estradiol in follicular development: During follicular development, follicles produce both testosterone (and several other androgens [male hormones]) and estradiol (plus small amounts of estrone). The androgens are produced in the theca cell layers. The theca cell layers are not able to convert these androgens into estradiol or estrone because they lack the necessary enzymes. Instead, through diffusion, these androgens enter the granulosa cell layer of the follicle where the necessary enzymes are found (aromatase) to convert testosterone to estradiol and androstenedione to estrone. A separate enzyme converts the estrone into estradiol within the granulosa cells. In conditions like polycystic ovarian syndrome (PCOS), there is an imbalance in the androgen and estradiol ratio with higher levels of androgens suggesting a problem with conversion of these hormones in that condition. We will revisit this in future articles on PCOS.

Ovulation

Progesterone prompts ovulation. Historically, it was thought that the LH surge caused the follicle to release the mature ovum (egg) in a reversal of the negative feedback loop between estradiol and the pulse of GnRH which suppresses release of both FSH and LH from the pituitary. New research suggests that the adrenals release a small surge of progesterone that stimulates ovulation and prompts a rise in LH. This pathway explains why women who are under stress experience delayed ovulation.

Based on my own at-home hormone monitoring of urinary metabolites of estradiol and progesterone plus LH and FSH, I can confirm this pre-ovulatory temporal rise in progesterone. In fact, if this new theory proves correct, it may help explain the sudden shift in the electrolyte composition of vaginal secretions at ovulation.

Progesterone concentrations just prior to ovulation are much lower than concentrations mid-luteal phase, and so it is likely that the adrenal cortex, rather than the developing follicles, are producing the progesterone necessary to prompt the surge in luteinizing hormone (LH). It is also of note that high concentrations of progesterone (like those produced during the luteal phase and during pregnancy) inhibit ovulation. In in-vitro fertilization, when progesterone is given at doses to simulate the blood concentration seen during the luteal phase, this prompts the “vanishing follicle” phenomenon suggesting that a low progesterone concentration is vitally important to successful ovulation.

This theory may also explain why women under stress do not ovulate. It is common for women who develop a cold or illness during the peri-ovulatory phase to have either delayed ovulation or an anovulatory cycle. Other forms of stress (mental, over-exercise, disturbances to the circadian rhythm) are also known to delay ovulation. Considering that pregnenolone is the precursor to both cortisol and progesterone, this progesterone rise theory as the key event leading to ovulation evolutionarily fits the concept of conserving eggs or preventing reproduction when conditions aren’t favorable to pregnancy. Elevated demands for cortisol during times of high stress would deplete the body’s ability to create progesterone.

Role of LH: LH (luteinizing hormone) transforms the follicle into the corpus luteum. While the follicle primarily generated the hormones testosterone and estradiol throughout follicular development and leading up to ovulation, the corpus luteum releases progesterone and estradiol to maintain the uterine lining after ovulation.

Key Takeaways From the Luteal Phase and Menstruation

Progesterone released by the corpus luteum throughout the luteal phase is vitally important for pregnancy because it sustains the uterine lining providing nourishment to the developing embryo until the placenta fully forms around 12 weeks gestational age. It is especially important that concentrations of progesterone be maintained until implantation of the fertilized egg occurs. Luteal phase deficiencies, which we will talk about more in future posts, is one of the common causes of implantation failure.

In the absence of pregnancy, the corpus luteum atrophies between 10 and 16 days after ovulation. As the corpus luteum atrophies, levels of progesterone and estradiol both fall, resulting in atrophy of the uterine lining resulting in onset of menses.

An Overview of a Healthy Menstrual Cycle

In summary, a slowdown in the rate of release of GnRH from the hypothalamus prompts an increase in FSH secretion from the pituitary and this awakens further development in antral follicles within the ovaries. As these follicles mature, both testosterone and estradiol are made by the developing follicles increasing the amount of both these hormones within the body. Estradiol quickens the release rate of GnRH by the hypothalamus which reduces FSH secretions by the pituitary gland.

Historically, it was believed that once estradiol achieved a critical threshold, this negative feedback loop reverses, and FSH spikes along with an LH surge to cause ovulation. New research shows a transient rise in progesterone ahead of the LH surge. This rise in progesterone is about one-tenth the maximum rise in progesterone seen during the luteal phase of the cycle and is presumably produced by the adrenal cortex. If this theory (that a transient concentration-dependent rise in progesterone) prompts ovulation, then this better connects the dots between why stress and undereating cause anovulatory cycles.

Luteinizing hormone, which spikes around the time of ovulation, elicits key changes within the follicle allowing for rupture of the mature egg from the follicle and conversion of the follicle into the corpus luteum. The corpus luteum produces both progesterone and estradiol and in the absence of pregnancy naturally atrophies resulting in falling levels of progesterone and estradiol. As circulating blood concentrations of these two hormones, which are necessary for maintaining the uterine lining fall when the corpus luteum atrophies, the uterine lining itself also atrophies and sloughs off the walls of the uterus leading to the onset of menses between 10 and 18 days after ovulation in a healthy cycle.

hormones across menstrual cycle — Figure 1. Hormone concentration throughout the menstrual cycle.

In Summary

This very quick overview of the menstrual cycle (aka ovulation cycle) forms the basis of every single fertility awareness method (FAM) today. Whether the method involves monitoring changes in cervical mucus, cervical position, basal body temperature, electrolyte composition of salivary/vaginal secretions, and/or at-home urinary hormone monitoring, these methods are highly reliable for predicting ovulation and are so reliable that their efficacy for avoiding unplanned pregnancy vies that of hormonal birth control.

These methods are also invaluable for shining light on a woman’s reproductive health and elucidating where hormonal imbalance lies within her cycle when things are a bit off. FAMs also provide real time data for women who are tracking their cycles so that you are able to adjust diet and lifestyle to support hormonal balance.

I will refer back to this article often in future posts on FAMs and hormonal health.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, and like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter.

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Hormones, Birth Control, and Insulin Resistance

by Brandy Searcy

Published on September 18, 2023

6145 views

Little known fact. Your reproductive hormones influence how your body responds to insulin. The artificial hormones in hormonal birth control also play a huge role in how your body responds to insulin. And, your body’s response to insulin determines how well you are able to use glucose to supply your daily energy needs.

In this article, we will discuss the basics of how your body creates energy. In this first section, we will unpack:

How your body creates energy from glucose
Glucose vs. fatty acids as an energy source
How insulin resistance impacts the shift between glucose burning and fat burning
How glucose enters your cells to become fuel for energy
How insulin resistance interferes with the transfer of glucose into your cells

Then, we will tie in how your natural reproductive hormones, estradiol and progesterone, impact your body’s use of glucose as a fuel source and discuss how hormonal birth control disrupts this natural balance.

How the Body Creates Energy From Glucose

Many of your cell types are designed to run on glucose, a metabolic product of carbohydrates, as their main source of energy, and in fact, certain cells that don’t contain mitochondria (or contain very few mitochondria) like red blood cells and cells of certain parts of your eye (lens, retina, and cornea) rely either exclusively (as is the case for red blood cells) or primarily on glucose as an energy source.

The reason for this is that mitochondria are responsible for aerobic (oxygen required) energy creation processes within your body, and cells with no or very few mitochondria rely mostly on anaerobic (no oxygen required) energy creation by glycolysis in the cytoplasm of the cell. As we will discuss in more detail later, when your body uses fatty acids as a fuel source, this pathway is purely aerobic, so it is not possible for fatty acids to be used in anaerobic energy creation processes within your cells.

When you eat a meal containing sugar (sucrose) or carbohydrates, enzymatic processes begin breaking the sugar and carbs down into their basic structures within your digestive tract. The structure of both sugar and carbs contain glucose.

Glucose fuels the creation of ATP in a process known as glycolysis, which happens within the cell, and through oxidative phosphorylation (OXPHOS), which happens within the mitochondria (substructures within the cell). When ATP is broken down within your cells, it releases energy, which is harnessed to power your mitochondria and other important cellular functions. The by-products of that ATP creation (pyruvate and ATP) fuel additional energy production cascades within the cell.

How the Body Switches From Glucose to Fatty Acids for Energy

Even when particular cell types prefer carbs (glucose) as their energy source rather than fatty acids, most cell types are capable of using either of these macronutrients (and also, when necessary, amino acids) as a fuel in order to survive periods of fasting (including overnight fasting).

Insulin plays a key role in regulating whether your body uses glucose (glycolysis in the cell’s cytoplasm and OXPHOS in the mitochondria) or fatty acids (lipolysis in the cell’s cytoplasm and fatty acid oxidation in the mitochondria) as its preferred fuel source. This is because insulin impacts the ratio of two key enzymes (malonyl Coenzyme A and acetyl CoenzymeA) that determine which of these energy pathways is preferred (here and here). The ratio of these enzymes is dynamic, changing throughout the day in response to when and what you eat, and in response to this fluctuating ratio, your body preferentially uses carbs (glucose) or fatty acids as its fuel source.

In an insulin resistant state, your body does not easily shift between glycolysis/OXPHOS (glucose as fuel) and lipolysis/fatty acid oxidation (fatty acids as fuel) and instead remains in a state of using fatty acids as fuel. We will talk about why this is the case in the next section.

How Glucose Gets Inside Cells

The glucose released in your digestive tract from the food you eat is absorbed into your bloodstream, and when your blood glucose levels start to rise following a meal (or any drink containing carbs or sugar), it signals your pancreas to release insulin.

Insulin is the messenger that lets your cells (specifically, your skeletal muscle, fat, kidney, and liver cells) know there is glucose available in your bloodstream. Insulin does this by binding to the cellular membrane, and this activates glucose transporters on the cellular membrane.

Once blood glucose levels start to drop, a healthy body clears insulin fairly quickly so that it can maintain adequate blood sugar levels. Insulin must be cleared so that blood sugar doesn’t drop too low.

What Is Insulin Resistance?

A number of factors influence how your cells respond to insulin. External influences (like stress, diet, and lack of sleep) along with internal factors (hormonal fluctuations) play a role in how the cells respond to insulin. And, different types of cells respond differently to insulin. Skeletal muscle cells are the most sensitive to insulin. Fat cells and liver cells are also sensitive to insulin, and so these cell types (skeletal muscle, fat, and liver) are the quickest to take up extra glucose from the bloodstream.

When your body becomes more insulin resistant, the cells are not as able to respond to insulin. My favorite analogy for this is to imagine that you are at a rock concert. You cannot easily hear the person next to you because the volume in the venue is so loud that your ears are overloaded by the background noise. In order to carry on a conversation, you must move to a quieter place. In this scenario, insulin is the background noise or the decibel level. When you are insulin resistant, your pancreas releases extra insulin to try to get your body’s cells to respond. This would be the same as somebody yelling at you in a concert hall so that you are able to hear them speak.

When you restore insulin sensitivity, it is like taking your body out of that loud concert hall and placing it somewhere quiet. Now, you are able to hear and carry on a conversation without any problems. When you restore insulin sensitivity, the cells are capable of responding to a much lower amount of insulin much more quickly and take the action of absorbing glucose from the bloodstream.

Insulin Resistance Begets Insulin Resistance

With insulin resistance, the cells are used to the high insulin environment (partially deaf to insulin), so they stop responding to insulin’s call. This prompts the pancreas to release more insulin in order to get your cells to hear the message to soak up the extra glucose circulating in the bloodstream. When insulin is unable to be heard because of the high background noise (because there is so much circulating insulin the cells are deaf to it), then glucose isn’t taken up by the cells. This then creates the false message from your cells to key organs to start releasing stored glucose (in a process called gluconeogenesis) to supply the body’s energy needs.

When we are talking about diabetes, this feedback loop often, but not in everyone with diabetes, results in a perfect storm of upward spiraling blood sugar levels.

insulin resistance cycle common in diabetes showing increased insulin resistance triggering gluconeogenesis resulting in higher blood sugar levels which increases insulin resistance — Figure 1. Insulin resistance begets more insulin resistance.

Even in conditions besides diabetes where blood sugar levels are dysregulated, you might have one condition (for example, insulin resistance), without the other (increased release of glucose from your body’s reserves).

With all of that in mind, let us take a look at how reproductive hormones impact insulin resistance and gluconeogenesis, the process of releasing glucose from stored reserves.

Estradiol, Synthetic Estrogens, and Insulin Resistance

Reproductive hormones play a key role in insulin resistance. Most scientific studies agree that estradiol (the endogenous estrogen produced primarily in the ovaries throughout the reproductive years) boosts the release of insulin from the pancreas. While at first glance, this looks like estradiol might contribute to insulin resistance because it prompts release of extra insulin, the opposite is actually true.

Estradiol is widely accepted as a potent compound to restore insulin sensitivity. Whether this is because of upregulation of insulin from the pancreas or whether it is also because of the influence estrogen has on the cells when it binds to estrogen receptors or a combination of both of these is not clear. What is clear, is that estradiol encourages cellular uptake of glucose and more rapid reduction of blood glucose levels after a meal. Estradiol also reduces gluconeogenesis in the liver suppressing the release of free glucose into the bloodstream from the body’s reserves, and this supports healthy blood sugar levels (here and here).

Estrogen Concentrations and Insulin Resistance

How estradiol affects insulin resistance is concentration dependent. Estradiol concentrations in the bloodstream within the normal circulating range (not more than 1 nanomolar abbreviated 1 nM) are associated with healthy insulin sensitivity and healthy blood sugar levels while concentrations higher than 1 nM are associated with insulin resistance. This may be why gestational diabetes is a common condition during pregnancy with up to 10% of pregnant women in America developing gestational diabetes. Progesterone also plays a key role in gestational diabetes as we will discuss in more detail below.

Non-bioidentical Estrogen and Insulin resistance

Ethinyl estradiol, the most common synthetic estrogen used in hormonal contraceptives here in America, also impacts insulin resistance, but like endogenous estradiol, the relationship is not straightforward. Ethinyl estradiol has been shown to impact insulin sensitivity and gluconeogenesis differently depending on:

its concentration in the hormonal birth control
what progestin (synthetic progesterone) it is paired with

Just as high concentrations of endogenous estradiol increase the chances of dysregulated blood glucose control, the synthetic estrogen, ethinyl estradiol, also increases chances of dysregulated blood glucose control. Chemical diabetes caused by hormonal birth control is also well documented in the literature. This is one of the reasons why, since the 1960s, the concentration of artificial estrogens in combined oral contraceptives has been dramatically reduced from upwards of 60 micrograms per pill to as low as 10 micrograms. Currently, most birth control options contain from 20 to 35 micrograms of ethinyl estradiol per pill.

Estrogen Binds to Insulin Receptors Affecting Insulin Resistance

Estrogens, whether synthetic or endogenous, affect blood sugar regulation differently at different concentrations because of their ability to bind to insulin receptors. This concentration-dependent effect of both endogenous estradiol and synthetic estrogens is often overlooked in the conversation regarding the impact of hormonal contraceptives on blood sugar control. Inasmuch as estrogens play a role in insulin sensitivity, insulin secretion, and in gluconeogenesis, and because estrogens are combined in hormonal contraceptives with a wide range of synthetic progestins, the effects on blood sugar regulation are quickly compounded and convoluted.

Progesterone, Progestins, and Insulin Resistance

As with estradiol, the concentration of progesterone also impacts whether progesterone improves or diminishes insulin sensitivity. It is generally accepted that higher concentrations of progesterone during pregnancy are a major contributor to gestational diabetes. Similarly, high concentrations of progesterone, even after menopause, are linked to an increased risk of developing type 2 diabetes.

The actions of progesterone on glucose metabolism is very much related to carrying a pregnancy to term, promoting glucose storage (rather than consumption of glucose for fuel) and promoting ketogenesis (fat burning) within the body. Even when not pregnant, progesterone is the dominant hormone during the luteal phase (second half of your cycle), and this effects how your body uses glucose and its sensitivity to insulin. This ties into common experiences during the second half of your cycle including carb cravings, potentially diminished appetite (if you are like me), and also weight gain.

Unlike artificial estrogens, of which there is only one used in the combined hormonal contraceptives available in the United States, for progestins, the synthetic forms of progesterone, there are four generations of progestins, with each generation containing progestins of different molecular structures. The class of molecules used in synthetic progestins are similar in structure to the endogenous progesterone molecule, but they are not the same. In other words, they are non-bioidentical.

Progestins bind differently to the progesterone receptors within the body (and also bind to a variety of other receptors), than the endogenous progesterone and their specific structure contributes to how much and whether insulin resistance increases. The molecular structure also affects how the body conserves glucose (increases glucose storage) or uses glucose (in the process of gluconeogenesis). It is generally believed that the androgenic nature of progestins determine their role in reducing insulin sensitivity (here and here).

Hormones and Body Composition

An interesting note, whether we are talking about natural reproductive hormones, estradiol and progesterone, or artificial hormones, ethinyl estradiol and the various progestins, these are all fat-soluble hormones. That means, these hormones may be stored in, and thus, impact the behavior of fat cells. One study evaluated the response of fat cells (adipocytes) in the presence or absence of treatment with artificial hormones and found that in the presence of artificial hormones, the adipocytes were more insulin resistant. This suggests that fat cells may serve as a reservoir for artificial hormones and endogenous hormones alike. They essentially soak up circulating hormones from the bloodstream, and these absorbed hormones in turn impact how the fat cells behave.

This finding means that body composition affects how you respond to hormones, whether endogenous or synthetic, and vice versa. It also suggests that, among other things, we ought to consider dosing hormonal contraceptives relative to body composition. Women with higher body fat may store more of the hormones than those with lower body fat and this may initiate or exacerbate insulin resistance.

Summary

In summary, reproductive hormones are intricately intertwined with metabolism, both with how the body creates energy and how it stores fats and carbs to meet energy demands between meals. Hormonal birth control impacts this finely choreographed dance between reproductive hormones and insulin sensitivity, and this seemingly small influence has a dramatic ripple effect. Insulin sensitivity dictates things like weight gain, oxidative stress, and even, as we will discuss in the next article, susceptibility to UTIs and UTI like symptoms.

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We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter.

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Women in Clinical Trials

by Chandler Marrs, PhD

Published on July 6, 2020

8969 views

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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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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This article was first published in 2013.

Promiscuous Hormones and Other Fun Facts

by Chandler Marrs, PhD

Published on November 19, 2018

8910 views

Every time I read about an environmental endocrine disrupting chemical, a medication or even sometimes actual endocrine research, I am amazed, dumbfounded by the lack of up-to-date information about how hormones and receptors work. Indeed, much of the research still operates on what is called the ‘classical’ view of hormone-receptor activity. And while, those functions are still accurate, there is so much more going on that merits understanding and investigation. Here are some basics that will blow your mind.

Understanding Hormones and Receptors

Hormones are gods. Like the gods of Greek mythology, hormones control everything. There is a not a physiological system that a hormone does not impact in some manner or another. And this is why ignoring hormones in health research is so bloody dangerous and just downright stupid.

Hormones bind to receptors. This isn’t mind-blowing, but is the basis for all endocrine and in fact chemical activity in the body – compound A has to talk to body part B. The conversation is mediated through receptor binding. The shape of the hormone determines which receptors and how strongly the hormone fits or binds. Much like a lock and key, only certain keys open certain locks.

Hormones are promiscuous. Hormones sleep around. Hormones like binding with other hormone receptors and are often similar enough in structure to do so, especially at higher concentrations. This means that estrogens will bind with estrogen receptors but also androgen receptors. Progesterone binds with estrogen receptors but also gluccocorticoid (cortisol) and mineralocorticoid receptors, and so on. Because of this cross-binding, the measure of interest becomes the hormone’s ‘affinity’ for a certain receptor. How much does hormone A like receptor B. The stronger the affinity, the longer it stays bound and the more intracellular effects it exerts.

The most shapely hormones bind more. Like mating, shape matters. The more shapely hormones bind to more receptors, more tightly. For example, the shape of MBP, the metabolite of BPA fits into the estrogen receptor better than BPA. In fact, MBP is a 1000 times stronger than BPA in its affinity for the estrogen receptors (ERs). If both MBP and BPA were competing for the affections an ER, MBP would win. This happens with all hormones and hormone-like chemicals, the more shapely the compound, the better it fits with a receptor and the longer it stays there.

Promiscuous hormones spread the love. The effects of an endocrine disruptor, even an estrogenic one may not be limited to the reproductive classics. Estrogen receptors are located all over the body and the brain, so too are androgen, progesterone, glucocorticoid, mineralocorticoid and thyroid receptors. So any time we talk about a hormone’s impact on health, we have to look at where its receptors are located. Ditto for chemical that binds to hormone receptors. And to make it even more complicated, because these hormones bind promiscuously, one also has to consider the fact that the hormone may act at other, non-similar receptors. Hormone promiscuity makes endocrine research infinitely more complex than asking whether hormone A binds to hormone receptor A or how long a substance takes to clear from the body.

Hormones beget more hormones. That’s right, hormones have babies and lots of them. Called metabolites, the offspring of one hormone can lead to a whole family of other hormones, each promiscuously binding with receptors. It’s a veritable orgy in there. How many and what type of hormone offspring depends entirely on the enzymes the hormone meets as it travels through the body. This means, it’s not enough to simply measure the effects of the parent hormone on health, but one has to look at its offspring or metabolites as well.

Take Home

Hormones systems are complicated. Hormone disrupting chemicals likely disrupt a myriad of physiological systems, often transgenerationally. One off, linear, cause-effect, dose-response studies cannot begin to understand the system changes involved with endocrine modulation. This requires large scale, data modeling tasks, that have yet to be designed. For the time being, any study that claims to have proven that a man made, endocrine disrupting chemical or hormone altering medication is completely safe or works only on the intended physiological system, is likely lying. They just haven’t found how or where the chemical is wreaking havoc. I’d err on the side of caution.

Image credit: Jan Saenredam, Public domain, via Wikimedia Commons

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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Image: Jan Saenredam; Public Domain

This article was first published May 3, 2013.

Sexual Function After Hysterectomy

by WS

Published on January 15, 2018

144625 views

Whether a hysterectomy will affect sexual function is a common concern amongst women considering the surgery, as well it should be. Sex is a vital part of life and the loss of sexual function can be devastating. Whether and how hysterectomy affects sexual function is not very clear, however, and depends upon a number of variables, not the least of which is sexual function pre-hysterectomy, and particularly, pre-gynecologic problems. In many cases, women have a hysterectomy to rectify conditions associated with heavy bleeding and/or excessive pain like fibroids, endometriosis, adenomyosis and cysts. Reducing pain and bleeding should positively affect sexual frequency; however, effects on function may vary. Hysterectomy can diminish sexual function either directly because of the disconnection of the nerves and blood vessels that supply sexual energy or indirectly via the loss of critical hormones when or if the ovaries are removed or cease to function. And for many women, those with endometriosis, the hysterectomy itself provides only temporary relief from the disease process.

When evaluating the possibility of having a hysterectomy relative to sexual function outcomes, there are a few things women must consider.

Understanding the “Anatomy” of Sexual Function

According to Masters and Johnson, there are four phases of sexual response – Excitement, Plateau, Orgasm, and Resolution.

Sensation to any body part requires proper nerve conduction and adequate blood flow. Many nerves, blood vessels, and ligaments are severed to remove the uterus. The uterus and its ligaments themselves are rich sources of blood supply. As a result, sensation to the vagina, clitoris, labia, and nipples can be diminished by hysterectomy. This loss of sensation can hamper sexual function.

The Excitement phase is triggered by sexual stimuli, either physical or psychological. The stimuli triggers increased blood flow (vasocongestion) to the genitalia. With a blood vessel and nerve network altered by hysterectomy, this process may be hampered.

Contractions of the uterus are listed as a part of the Orgasm phase. So without a uterus, orgasm is not complete. Hence, it would make sense that orgasm is negatively impacted by hysterectomy, ovary removal or not. I have read, however, that some women do not experience uterine orgasm. So for them, a hysterectomy may not affect their orgasms.

My Personal Experience Post Hysterectomy

I realized very quickly after my hysterectomy that my libido, arousal, and ability to orgasm were broken. A steamy sex scene in a novel or movie or a hot looking guy no longer elicited sexual feelings. And the thought of sex was repulsive. That was a very sad day for me and I still mourn the loss of my intact sexuality. Some may question whether these changes are really due to the loss of my uterus or more so from the loss of my ovaries. When my hormone replacement was inadequate, the thought of sex was repulsive. However, I did have occasional orgasms but they were difficult to achieve and very infrequent as well as disappointing compared to before hysterectomy. Before my surgery, I had a good libido and an intense uterine orgasm every time I had intercourse. I have been on a good hormone regimen for over 6 years now. Sex is no longer repulsive but I do not have a libido or feel sexual in any way. Arousal takes much longer and orgasms are still weaker than before hysterectomy, do not always happen, and rarely occur during intercourse. Testosterone did not improve libido or arousal nor improve orgasm frequency or quality. Nipple sensation has been absent since surgery. These losses to my sexuality have affected my marriage relationship as well as social and professional relationships as I lack what I would call “sexual energy” and confidence.

Hysterectomy and Sexual Function

Why is it that so many dismiss sexual problems post-hysterectomy as psychological? If a man has his prostate and/or testicles removed or penis shortened (heaven forbid!), sexual problems are attributed to the loss or surgical alteration of his SEX organ(s). So why would it be any different for women?

Although there have been some studies on sexual function after hysterectomy, I have not been able to make much sense out of them. It seems that most use a benchmark of (impaired) sexual function shortly before hysterectomy when gynecologic problems impede sexual activity and function versus prior to the gynecologic problems that are the reason for the hysterectomy. This observational study compared sexual pleasure, activity, and problems by type of hysterectomy at 6 months post-operative. It concluded that “sexual pleasure significantly improved in all patients, independent of the type of hysterectomy.” However, it also concluded that “the prevalence of one or more bothersome sexual problems six months after vaginal hysterectomy, subtotal abdominal hysterectomy, and total abdominal hysterectomy was 43% (38/89), 41% (31/76), and 39% (57/145), respectively.” With these high rates of “bothersome sexual problems” I cannot imagine how this could have been an improvement. However, if the benchmark was based on the time frame when pre-operative heavy bleeding, discomfort, or pain impaired sexual activity and function, then it would certainly be possible for sexual function to improve post-operatively. That does not mean it was an improvement over NORMAL sexual function (pre-gynecologic problems).

This Boston University School of Medicine article discusses post-hysterectomy sexual dysfunction. It says,

“Desire, arousal, orgasm and pain disorders may all be seen post-hysterectomy…..Internal orgasms are often changed significantly after hysterectomy. This is observed in part due to the inability to have rhythmic contractions of uterine muscles without the uterus present. Also, internal orgasms are changed after hysterectomy due to injury to the nerves which pass near the cervix. Surgeons should try to spare these nerves, but efforts to spare them are limited at the present. The result is that after hysterectomy, many women lose the ability to have an internal orgasm.”

Changing the Mindset: Removing a Woman’s Sex Organs Impairs Sexual Function

First and foremost, we need to stop referring to women’s sex organs as reproductive organs since they have vital, lifelong functions far beyond reproduction. In addition to the sexual functions, these include endocrine/hormonal, bladder and pelvic floor and anatomical and skeletal as detailed in my articles and the HERS Foundation’s video.

Secondly, women need to be more open about the effects hysterectomy has had on their health and quality of life, sexual and otherwise. It seems that some do not connect their problems with the surgery and many others choose not to talk about it. Before surgery, we are likely to believe that hysterectomy is fairly harmless since it is such a common surgery (second to c-section). No surgery is harmless. One that removes a woman’s sexual organs cannot help but cause problems with sexual function.

Some other factors that may be in play are that women seem to value their sex lives less than men. We tend to shortchange ourselves in other areas as well, putting others’ needs ahead of our own. Women of older generations were taught to trust and obey authority figures. So we typically trust our doctors and follow their recommendations. We are particularly vulnerable with gynecologists as we tend to have a long history with them through annual well woman checkups and pregnancies and deliveries. We are easy prey for hysterectomy marketing.

Clearly, there are far too many women being harmed by unwarranted hysterectomies and castrations. According to this 2000 study, 76% of hysterectomies do not meet ACOG criteria. Yet the rates have not declined and the use of robotics seems to be fueling even more hysterectomies with promises of quicker recoveries. Hysterectomies are big business with revenues rolling in to the tune of over $16 billion annually. With so much money at stake, we cannot count on the medical establishment to restrain themselves. It is up to us to spread the word.

Does Hysterectomy Affect Sexual Function?

Yes, it does. How can it not, given the nature of the surgical procedure? Whether the effects are generally more negative or positive is not clear. It largely depends on the reason for the hysterectomy including the severity and prolonged nature of those gynecologic problems. There is very little research and even less consideration or conversation regarding women’s pre- and post- hysterectomy sexual functioning. That is something we can change together by sharing our stories and communicating our needs.

Additional Resources

I highly recommend the non-profit HERS Foundation’s video “Female Anatomy: the Functions of the Female Organs.” It taught me most of what I know about the consequences of hysterectomy and/or ovary removal (castration). When I first discovered the video, some of it did not make sense. But as more time elapsed, the changes became clearer. My body and life have changed in ways I never could have imagined. I only wish I had found the video prior to my unwarranted hysterectomy.

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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This article was published originally on April 10, 2014.

From DES to the Pill: Are We Doomed to Repeat History?

by Mike Gaskins

Published on November 13, 2017

5439 views

“The doctor wouldn’t have given it to me if he thought it was dangerous, right?”

My wife asked this salient question as we discussed the pros and cons of The Pill. It sent us both into deep reflection. Everything we read said The Pill was dangerous, but the doctor had acted like they should come in a Pez dispenser. To this day, I’m not sure where the cognitive began and the dissonance ended.

The DES Debacle: Origins of Obstinance

Doctors are generally dogmatic, but their nearly universal laissez-faire attitude toward The Pill seems particularly paradoxical when you study the scope and seriousness of its side effects. How can doctors believe that The Pill is safe, when tomes of studies suggest otherwise? Research links The Pill to everything from breast cancer and strokes, to Crohn’s Disease and lupus. To understand where we are and how we got here, it’s important to study the journey that brought us here.

By 1970, the current dogma that ‘The Pill is safe’ was well rooted in the medical community. However, enough doctors expressed concerns that Senator Gaylord Nelson decided to hold Congressional Hearings on the matter. The big three networks covered the hearings extensively, which caused great anxiety among women taking The Pill — and even greater anxiety among pill proponents, who subsequently demanded more ‘pro-pill’ doctors be included.

Senator Nelson took umbrage with their complaints, noting that all but one of the previous doctors had actually been ‘pro-pill’ to some extent, but all had reservations about its complications. Nonetheless, many of the doctors in the second round of hearings seemed more decidedly ‘pro-pill,’ including Dr. Kenneth Ryan, who stated,

I know of no information that indicates that biological properties of the estrogens used in the contraceptive pill are any different than stilbesterol for which we have at least 30 years of clinical experience…(Competitive Problems in the Drug Industry, Ninety-First Congress, Second Session, Page 6541)

Very reassuring… Unless you were actually familiar with the 30-year history of stilbesterol, also known as diethylstilbestrol (DES). Sir Charles Dodds discovered DES in 1938, and rushed it to market in the public domain. The English doctor bypassed the patent process hoping it would discourage the Nazis from further tests on women prisoners in their development of ethinyl estradiol (Barbara Seaman, The Greatest Experiment Ever Performed on Women; page 36).

From DES to the Pill

Despite his noble intentions, Dodds soon regretted the decision. Without a patent, drug companies around the globe were free to produce DES. He never expected that synthetic hormones would be given to healthy women, and was horrified that doctors were prescribing it as hormone therapy for natural menopause.

You Can’t Put the Hormones Back in the Tube

Even worse, Dodds soon learned that an American doctor named Karnaky had begun blazing a new trail – doling out DES to ‘prevent miscarriages’. Alarmed by the news, Dodds sent him a study he had personally performed, which showed that the drug actually caused miscarriages in animal subjects. It didn’t deter Dr. Karnaky or the many doctors who followed his lead. (Robert Meyers, D.E.S. The Bitter Pill; pp. 56-73)

Dodds began to feel like he was fighting a monster that he himself had unleashed. He was most concerned about how his discovery could affect certain cancers. He sent DES samples to the newly formed National Cancer Institute in the United States, and urged them to conduct tests and notify doctors.

Dodds wasn’t alone. The Council on Pharmacy and Chemistry warned,

…because the product is so potent and because the possibility of harm must be recognized, the Council is of the opinion that it should not be recognized for general use at the present time…and that its use by the general medical profession should not be undertaken until further studies have led to a better understanding of the functions of the drug. (Barbara Seaman, The Greatest Experiment Ever Performed on Women; page 44)

The concerns sent murmurs through the medical community, and many doctors began experimenting with lower doses of DES. By 1940, the editors of the Journal of the American Medical Association (JAMA) felt compelled to add theirs to the litany of warnings:

“It would be unwise to consider that there is safety in using small doses of estrogens, since it is quite possible that the same harm may be obtained through the use of small doses of estrogen if they are maintained over a long period.” (JAMA, April 20, 1940)

In 1959, the FDA determined the link to side effects (including male breast growth) was sufficient to ban poultry farmers from using DES as a growth hormone. However, the widespread use of DES in humans continued. In fact, it had become standard medical practice by the time Dr. Ryan assured Congress that The Pill was just as safe as DES – showing how medical dogma often trumps scientific evidence.

The greater irony of Dr. Ryan’s statement materialized one year after his testimony, when researchers first linked a rare vaginal cancer to the daughters of women who received DES during pregnancy. The FDA reacted strongly, listing pregnancy as a contraindication for DES use.

Consumer Groups Take the Lead

You would expect this to be the beginning of the end for DES. Shockingly, the medical community responded with indifference, continuing to prescribe DES for a variety of ‘off label’ uses, including as a morning-after pill, to catalyze the onset of puberty, and the old faithful, hormone replacement therapy. (Robert Meyers, D.E.S. The Bitter Pill; page 185)

It took nearly a decade of passionate effort from consumer movements like DES Action to convince doctors to (mostly) abandon DES. Dozens of lawsuits were filed; some were settled; and some are still pending. There is evidence that the harmful consequences could now be affecting a third generation of DES victims.

The current Director of Epidemiology and Biostatistics at the National Cancer Institute, Robert Hoover, M.D. oversees the DES Follow-Up Study to track the ongoing repercussions. With identifiable problems now affecting the grandchildren of women who took DES, the disaster hasn’t yet moved into the past tense of our nation’s history. Despite that, Dr. Hoover says:

There’s essentially a whole generation of medical students who don’t know the story. The story has such powerful lessons that I think that’s a tragedy…For about 20 years now, when I standardly ask in my general epidemiology lecture… how many of you have heard of DES, nobody raises their hand.

Sidney Wolfe, M.D., who headed up Ralph Nader’s Health Research Group offered this perspective,

DES is an excellent example of how drug companies behave, how they take advantage of the ways doctors act, and how they make millions of dollars by ignoring evidence of a drug’s harmfulness, by failing to get evidence that it is effective, and then by marketing a product that plays on fears and misconception. (Robert Meyers, D.E.S. The Bitter Pill; page 208).

In just 20 years, the American Medical Association moved from “It would be unwise to consider that there is safety in using small doses of estrogens…” to embracing the release of insufficiently tested hormones as birth control for millions of women. I’m leery of trusting a dogma founded on such an erratically moving target. In their defense, the dogma really hasn’t moved much in the decades since.

Today, the medical community assures us The Pill is the most researched drug ever. Sorry doc, that reassurance just doesn’t ring true. At this point, it feels more like a phrase learned by rote than a statement based on any kind of empirical evidence. Unfortunately, it’s not the only hollow mantra that should raise a red flag when it comes to hormonal contraceptives. I will discuss how the medical community responds to scientific studies in my next post, The Spin Doctor’s Prescription for Birth Control.

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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This article was published originally on Hormones Matter on August 31, 2016.

It’s Not All In Your Head: Mental Health and Hormonal Birth Control

by Kerry Gretchen

Published on August 22, 2017

10001 views

Once upon a time, a 26-year-old woman went to her doctor and asked to be put on the new birth control pill that allowed women to only have four periods a year. She had seen it advertised on television. Four months later, 15 pounds heavier and suffering from mild depression, she returned to the doctor feeling miserable. The doctor told her the weight gain and depression were not from the pill because those were not side effects of hormonal birth control. Wait, does this sound familiar? It’s the same story I told in my article about hormonal birth control and weight gain. Only this time, I’m talking about mental health.

The truth is that I gave my mood changes and my mild depression very little thought. Once the doctor told me they were not a symptom of my new birth control pills, I figured it was my fault I was sad and not dealing with things very well.

What They Knew in 1970

I remembered the connection between my birth control pills and that bout of depression when I began reading the Nelson Pill Hearings. One of the first doctors to testify pointed out that there had been a suicide during the original pill trials in Puerto Rico. Neither the suicide, nor the other three sudden deaths (of five total deaths during the experiments) were investigated. But what really got my attention was that the page after the mention of the suicide was the only one missing in the nearly 1500 pages of testimony. I have since been able to get a copy of that page and while the testimony doesn’t seem that damning given the laundry lists of risks, concerns, and dangers with hormonal contraceptives that are examined at the hearings, it does bring up an interesting point.

Doctor Edmond Kassouf’s testimony answers questions from Mr. James Duffy, minority counsel at the hearings (page 6112):

Mr. Duffy: One of the five deaths was suicide.
Dr. Kassouf: Yes.
Mr. Duffy: So what I would like to understand is how does one take a suicide and link the case of death to the pill?
Dr. Kassouf: Very simply. It has been of current concern. Many physicians and psychiatrists are concerned about depression and the pill. If this is true, suicide may well be the end result of that combination and, therefore, a reasonable suspect, a reasonable link.

Suicide Attempts While on the Pill

“I’ve really got to look into this more,” I thought. Well, I had to look no further than page 6447 and the testimony of Dr. Francis Kane, Jr., Associate Professor of Psychiatry at the University of North Carolina. To sum up his testimony about the studies conducted with regard to mental health and oral contraceptives, he says this (page 6457):

“There is considerable incidence of mild to moderate psychiatric morbidity [disease] associated with the use of combination oral contraceptive agents… In three of the four studies, there seems to be agreement that those who have required psychiatric care in the past will be more at risk for the development of morbidity, including psychosis. One study also suggests that there may be some increase in the depth of illness the longer the medication is taken.”

Dr. Kane describes a study conducted in England of 50 women on oral contraceptives who were compared to a control group of 50 women who had not used hormonal contraception. There were no differences in socioeconomic status, age, or history of past depressive episodes. But in the group taking the pill, 14 women “had depression of mild to moderate proportions, while only three of the control group reported this.” The pill users also reported greater depression as well as particularly high scores for “guilt, self-absorption, and loss of energy.”

He goes on to say, “Two suicidal attempts in the pill sample were found, which had not been disclosed to the general practitioner. Since completing the study, another depressed pill-taker had made a serious suicidal attempt.” Three suicide attempts in a study of 50 women? That seems incredibly high to me. Ludicrously high. Especially given that there are other methods of contraception.

But Wait, There’s More!

But that’s just one doctor testifying about a few studies, right? Sure. But the next person to testify was Dr. John McCain (not the senator). One of the first things the doctor points out is (page 6471):

“The contraceptive pills are potent steroid hormones. Alterations of the anterior pituitary function are produced by them… the potential endocrine and systemic disturbances are almost unlimited. The effects produced through the anterior pituitary may be so indirect that years may elapse before a correlation is established between the abnormality and the administration of the contraceptive pills.”

You know what else is a hormonal medicine? Anabolic steroids. “Roid rage” is pretty well documented. Is it really such a leap to think that hormones in birth control can also cause changes in mental health?

Dr. McCain spent years documenting the patients in his practice who suffered serious side effects from hormonal contraception. In that time, he recorded episodes from 52 patients. And per his own testimony, his largest concern was mental health (page 6473).

“The emotional or psychiatric problems are the complications which seem to me to have the most serious potential danger. Three patients have stated that they were desperately afraid that they were going to kill themselves… After the pills were omitted, the depression and suicidal fears of the three patients disappeared, as did the depression of the other patients.”

He also points out (page 6473):

“It is disturbing to consider the patients on the pills whose depression may have ended in suicide and/or homicide with no recognition of any association with the contraceptive pills… Personality changes could be a factor in other conditions such as automobile accidents and divorces.”

Is it really so much of stretch to think that a potent steroid could cause personality changes that could lead to the damaging of personal relationships that are beyond repair? Plenty of other potent substances can and do.

What They Say Now

Dr. Kane and Dr. McCain, as well as every other expert who testified at the Nelson Pill Hearings, agreed on one thing. More research was needed.

So what does the research say now?

Medscape published an article from the American Journal of Epidemiology with the claim that “Hormonal contraception may reduce levels of depressive symptoms among young women.” Yet when you read further into their conclusions, they say that nearly one-third of women discontinue hormonal contraceptives within the first year, many because of mood changes, and those women are unlikely to restart hormones. Therefore, “hormonal contraceptive users at any time point may be overselected for less depression than nonusers.”

The study also points out that:

“Existing literature on hormonal contraception and depression has been primarily confined to small, unrepresentative samples. Among these smaller studies, few cohesive findings have emerged.”

And:

“Little research has examined the role of exogenous hormone use in suicidality, and existing research has focused on mortality from suicide rather than suicide attempts.”

And according to WebMD, there are a laundry list of medications that can cause depression. What is not included on this list? Birth control pills. The only hormonal contraception included is Norplant. Interestingly enough, the active ingredient in Norplant is levonorgestrel, a progestin found in many birth control pills as well as hormonal IUDs. So am I supposed to believe that when injected into my arm, synthetic hormones can cause me depression but when taken daily as a pill or sitting in my uterus for 5 years, they won’t? Does that make any sense at all?

It doesn’t make sense to Dr. Kelly Brogan. That’s why when she has patients that complain of depression, anxiety, low libido, mood changes, weight gain, etc. she recommends they stop using hormonal contraception.

What Have We Learned?

Hormonal contraceptives can cause mental health issues
Women who suffer from mental health issues are much more likely to suffer from increased symptoms when on hormonal contraception
Often the longer hormonal contraception is used, the greater the symptoms
Discontinuation of hormonal contraception can usually alleviate mental health symptoms
The research promised from the Nelson Pill Hearings has never materialized

Why, if they knew in 1970 that hormonal contraception was deeply connected not only to depression but also to suicide, has it not been further researched? It’s been nearly 50 years since Dr. Philip Ball (page 6493), a specialist in internal medicine, testified before congress. Which makes what he says all the more chilling.

“It is not considered reasonable that there be any mortality or morbidity in a pill used purely for contraception purposes. Medical research has got to offer something better than this. Physicians will probably look back on the contraceptive pill era of the past 5 years with some embarrassment.”

Exactly.

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Image by jcomp on Freepik

This post was published originally on Hormones Matter on June 22, 2016.

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