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From the Townsend Letter
February / March 2016

Oxytocin: The New Hormonal Kid on the Clinical Block
by Dr. Devaki Lindsey Berkson
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Modern Dilemma
In America today, marital relationships and personal moods seem pretty hard to hold together. Fifty percent of marriages end in divorce.1 Studies say that 20% to 72% of husbands commit adultery and 10% to 54% of wives do likewise.2 Try as we may to achieve happy relationships, many fail.3
Moods are murky. Anxiety disorders affect 40 million adults and cost one-third of all monies spent on mental health. The National Center for Health Statistics shows that 1 in 10 Americans (and 1 out of 4 women in their 40s and 50s) take antidepressants.4
What if there was a safe nasal spray (of all things) that could enhance relationship harmony and loyalty, heighten desire and orgasms, stabilize moods, and make us feel more right with our world? 5-8 What if it wasn't addictive? And didn't have rebound issues?

Enter Oxytocin
In science, this hormone is referred to as the official neuropeptide of "attachment." This article brings you up to snuff (the bulk of research on oxytocin is on the intranasal delivery mode) on the clinical applications of oxytocin replacement. You will learn that it is a team player with our sex steroid hormones, our ability to be lean and not mean, and as part of the Buddha (vagal) pathway between the brain and gut.9
Oxytocin is a peptide hormone. Peptide hormones are made of amino acids. A peptide is a link of two or more amino acids. As far as peptide hormones go, oxytocin is a small thing, with only nine amino acids. In comparison, thyroid-stimulating hormone (TSH) contains 201. Sometimes oxytocin is referred to as a nonapeptide, since nona means "nine."
Oxytocin is historically appreciated for its role in pregnancy. It signals uterine contractions, lets down milk for lactation, and deepens bonding between mother and child.10,11 But there's more. Emergent research and clinical evidence reveal ever-expanding possibilities for oxytocin replacement in the clinical trenches. For example, oxytocin therapy is being used to treat autism spectrum disorder, schizophrenia, obesity, addiction, erectile dysfunction, and orgasm disorders, and as a libido, orgasm, and emotional "bonding" enhancer.12-14
Viagra has become a household word. It's an effective, best-selling sexual medication. Viagra has also been looked at for treating depression and other mental disorders.15,16 Why? It boosts oxytocin production.17

Oxytocin Receptors
Hormones are signaling molecules, or "e-mailers" in the body's physiologic Internet system. Hormones are made in various organs throughout the body. For example, oxytocin is made in the brain. These hormones are then secreted into the watery highways of the blood, where they swim to specific tissues in search of perfectly fitting receptors. Receptors are proteins shaped like malleable satellite dishes. Hormones swim into their exact receptor. Once inside, the hormone docks into specific binding domains. Marching orders are delivered to genes. Based on these directives, cells take action.
Much of the cross-talk communication that takes place to nudge life to unfold is due to hormonal (ligand to receptor) and genomic (delivering to genes) signaling. There are other forms of signaling, such as receptor-free and nongenomic signaling, but they are beyond the scope of this article.
Oxytocin (OT) delivers messages to specific oxytocin receptors (OTR). We have oxytocin receptors globally in our human biologic real estate, not just in reproductive tissues. I have been using oxytocin replacement in practice for 5 years and have some startling case histories as well as some duds. Five summaries are presented later in this article.

Oxytocin is produced in the hypothalamus.18 It is made by the neurons of the paraventricular and supraoptic nuclei of the hypothalamus (the same areas of the brain turned on by orgasm; the bigger the orgasm, the more these cells are "turned on").19,20 These hypothalamic neurons have axons that deliver OT both locally and peripherally.
The brain has high levels of OTRs to receive a wide array of signals. Oxytocin acts as a neurotransmitter signaling the amygdala (seat of faith vs. fear), the nucleus accumbens (sense of well-being), and the hippocampus (home of short-term memory and confidence).21 Oxytocin traverses cerebral regions by diffusing across neural tissue, like you would cut across lanes to get to an off-ramp on a freeway.22 There are OTR receptors throughout the entire spinal cord.23

Animal model research emphasizes a strong relationship between the expression of OT in the brain and the ability to have socially monogamous attachment behavior. These investigations began with the vole. It's amazing research.
Two closely related species of voles have exact opposite relationship styles: one is monogamous, mating for life, while the other is promiscuous, choosing to be a forever player. What's the biological difference? The monogamous prairie vole has many more oxytocin and vasopressin (a playmate with oxytocin) receptors and activity in the brain. In comparison, the polygamous vole has far fewer such bonding receptors, and thus, more sleuthing mating behaviors.
Researchers have gone to the trouble of reversing these mating behaviors. They accomplished this by reengineering Mother Nature. By altering OT genes, they could morph typically promiscuous male voles into becoming devoted monogamous voles, and mate-for-life type voles into tomcat types. How? They altered the numbers of oxytocin genes. By reducing or increasing oxytocin signals (and its cohort, vasopressin) in the brain, they could reproducibly alter biologic desire for either monogamy or bigamy (though some say this should be dubbed "pig-amy").24,25
Moving forward from these findings, Young and Wang manipulated three attachment hormone musketeers (oxytocin, vasopressin, and dopamine) and influenced preference of one beloved over another. They "gene-jury-rigged" whom the animals would choose to mate with. They named this the neurobiological model of pair bonding.26 A number of researchers have pleaded the case that this is how humans basically meet, mingle, and mate, too.27,28
We know that moms and babes bond through oxytocin. Magnetic imaging of the brains of mothers who see photos of their own infants (compared with pics of matched control infants unknown to them) show that the areas of the brain that "activate" are flush with oxytocin, vasopressin, and dopamine receptors.29
It's clear. Oxytocin deserves to be called "the cuddle hormone," "the love hormone," or "the cuddle chemical."

Oxytocin helps buffer stress. It has hormonal influence over the hypothalamus/pituitary/adrenal axis (HPA axis). At various levels OT helps the host cope with stress and promotes anti-anxious reactions.30 In other words, OT signaling reduces the font size of suffering caused by stress.

Sex Hormones and Oxytocin
Sex steroid hormones – estrogen, testosterone, and progesterone – intimately interact with OTR and are part of sex hormonal influence over human emotions. Estrogens act synergistically with OT by enhancing its anxiolytic effects and increasing OTR levels. A single dose of estradiol increases plasma OT levels in women (one of the many reasons that estrogen replacement makes many women enjoy happier moods and avoid antidepressants) and a metabolite of testosterone (nicknamed 3beta-diol) has similar input in the brain and other critical areas, such as within the HPA axis.

Estrogen Receptor β
Estrogen has two major receptors that receive estrogen signals: ER alpha and ER beta. ER beta is an oncogene suppressor (protects against cancer) and anti-inflammatory molecule balancing out the pro-growth signals of ER alpha. Areas in the brain with OTRs stunningly overlap with exactly where ER beta-receptors live.32
Activation of ER beta normalizes HPA axis activity and acts to buffer stress and anxiety. Approximately 85% of OT neurons in the pituitary coexpress ER beta! There is grand crosstalk between OT and ER beta throughout the body. The multiple interplays are just now being explored. I prophesy that the "good" and "bad" roles of oxytocin and estrogen receptor beta will takes twists and turns because in some cellular places (such as the breast, prostate and brain), ER beta dominance (having many of these receptors) is what we want for tissue protection, but in other conditions (such as endometriotic implants and dysfunctional endothelium) this is not the case.
There also appears to be a "threesome" between a metabolite of testosterone (3B-diol – itself a promoter of ER beta) and ER beta and OT. All three synergize, especially in the brain and the vagus nerve.

Vagal or Buddhist Nerve Highway
In utero, when the fetus is developing, a mass of cells that are to become our brain and gut divide in half, and one cellular clump travels northerly to the brain and the other southerly to the gut. What connects the two throughout life is the vagus nerve. It's the second largest nerve system after the spinal cord. It's the longest cranial nerve, extending from the brain to the gut and other crucial organs. It starts in the brainstem behind the ears, travels down each side of the neck, across the chest, and throughout the abdomen. It connects the brain to the stomach and digestive tract and many other organs such as the lungs and the heart.
The vagus nerve is a bundle of multiple thousands of nerve fibers, of which 80% are sensory, meaning that these nerves report and reinforce back to the brain what's going on in the gut and the rest of the body. It's cellular Big Brother. The vagus nerve is a crucial part of the parasympathetic nervous system (though some is sympathetic, too). It is mostly the opposite of flight and fight.
Healthy vagal tone creates calm. Everyone has their own vagal footprint. The better the vagal tone, the less ruffled we are by stress and the more cast-iron stomachs we seem to enjoy. A healthy digestive tract is mostly parasympathetically "vagal."
The healthier your vagal tone, the lower your level of cellular inflammation, or the faster you bring inflamed tissues back to normal after infection, or the more peaceful your moods or the faster recovery back to calm after an emotional storm has hit.33
Oxytocin appears to be a major hormone player traveling vagal highways, maintaining calm, hormonal satiety and peace, suppressing inflammation, and more.34 Being a hormone of connectivity, oxytocin upregulation in the vagal nerve – this massive internal feedback loop –  may be part of feeling well and right with the world. Meditation boosts vagal tone and oxytocin.35
Again, crosstalk abounds. The vagus nerve is not only flush with oxytocin receptors, this large feedback nerve also influences the number of estrogen receptors in the nervous system and brain.36 Remarkable!

Romantic Love
Adults shown photos of a romantic partner with whom they are "intensely in love" light up brain areas flush with oxytocin, vasopressin, and dopamine receptors.37
A number of studies have looked at mating under experimental conditions, before and after orgasm, and when giving couples nasal administration of oxytocin, which delivers it directly to the brain. These have been done in both observational manners (not randomized controlled) and in double-blind, placebo-controlled scientific experimental design. These studies are where the hormonal rubber meets the enhancement effectiveness road.
Oxytocin replacement has been shown to create more pleasurable orgasms and a stronger sense of empathy in both men and women. Men given OT intranasally report the biggest bang, perhaps since during orgasm they naturally make less oxytocin than women, so any bump up might be more noticed.
Since men produce less oxytocin, a bonding hormone, they are less vulnerable to intimacy attachment compared with women.38,39 The highest experimental recorded levels of oxytocin, by the way, were shown to be achieved in women who were multiorgasmic.40 The more oxytocin, the more orgasms – if a woman is capable of having these types of releases. (My theory is that all women are capable, but not all are hormonally replete, or in shape emotionally or physically, or they or their partners have simply not been taught how. I have a new book coming out that outlines exact details.)

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