1971 vintage Valium ad targeted at women

There is a reason why women have been so heavily targeted in the marketing of GABAergic sedatives over the last century, and it’s not because they’re all crazy.

The female reproductive system is saturated with endogenous (naturally occurring, produced by the body) biochemicals – hormones, neuroactive steroids and their metabolites – that act as natural sedatives and benzodiazepines in the brain and central nervous system. [1]

They include, but are not limited to:

  • Progesterone
  • Estrogens
  • Neuroactive steroids (allopregnanolone, et al.)
  • Metabolites of these

As a result of fluctuations in these biochemicals, there occurs a phenomenon of both a progesterone withdrawal syndrome and a GABA-A receptor desensitization [7] effect that is similar in nature to the benzodiazepine withdrawal syndrome (BWS). It occurs in some women who are affected by PMS, PMDD, post-partum depression/psychosis, menopause and hysterectomy, and in sedative-hypnotic withdrawal syndromes.

This neuroactive-steroid connection may prove to be involved in sedative-hypnotic actions, aging, stress, and alcohol abuse. The steroids derived from progesterone may help explain the symptoms of pregnancy and menstruation, and perhaps one of psychiatry’s oldest conundrums: why men and women have such a striking difference in the incidence of anxiety and mood disorders. – George Koob, Ph.D., a professor of neuropharmacology at the Scripps Research Institute in La Jolla, California. [5], [8]

Because of these fluctuations in the neurosteroids and their metabolites, a temporary increase in concentrations of a molecule known as alpha-4 is produced, and this molecule will temporarily blunt the GABA receptor’s sensitivity to GABA (and GABAergic sedatives, including benzodiazepines) [6] until the hormonal state changes or fluctuates again. The phenomenon of increased alpha-4 can occur in men experiencing physical stress, but it is naturally more common at certain points in female menstrual and reproductive endocrine cycles.

Abrupt discontinuation of use of sedatives such as benzodiazepines and ethanol can also produce PMS-like withdrawal symptoms. [2]

Progesterone, allopregnanolone and many of their metabolites were found to be cross-tolerant with benzodiazepines, so fluctuating levels of these naturally occurring biochemicals can make for a bumpy ride for women during a benzodiazepine taper and recovery process. In a non-benzodiazepine affected individual, the interactions of these naturally occurring bodily processes aren’t often noticed, and if they are, it’s usually evident in women who suffer from PMS, PMDD, menopause, and post-partum and post-hysterectomy complications. It can look a lot like the benzodiazepine withdrawal syndrome. In women with epilepsy who are susceptible to the pro-convulsant effects of estrogen (possibly due to its glutaminergic excitatory effects on the central nervous system) seizures as a consequence of catamenial epilepsy (an epileptic seizure disorder associated with the menstrual cycle) may result. [3] With this in mind, hormone replacement therapy should be approached with caution in women suffering BWS, hormonal disorders and in women with epilepsy. An understanding that progesterone is a GABAergic biochemical which can have a withdrawal syndrome similar to BWS should be known. Some women may prefer to taper when they discontinue progesterone therapy. [3]

Benzodiazepines can increase risk of birth defects and complications during pregnancy and breast-feeding

Unsurprisingly, babies born to drug-addicted mothers suffer from potential birth defects and complications. Benzodiazepines are no exception, even in mothers who are prescribed a benzodiazepine and take it responsibly, without addiction or substance use disorder.

From the Ashton Manual:

Benzodiazepines actively cross the placenta and, when taken regularly during pregnancy (even in therapeutic, prescribed doses) can cause neonatal complications. The foetus and neonate metabolise benzodiazepines very slowly, and appreciable concentrations may persist in the infant up to two weeks after birth, resulting in the “floppy infant syndrome” of lax muscles, oversedation, and failure to suckle. Withdrawal symptoms may develop after about two weeks with hyperexcitability, high-pitched crying and feeding difficulties. Benzodiazepines in therapeutic doses appear to carry little risk of causing major congenital malformations. However, chronic maternal use may impair foetal intrauterine growth and retard brain development. There is increasing concern that such children in later life may be prone to attention deficit disorder, hyperactivity, learning difficulties, and a spectrum of autistic disorders.

Benzodiazepines are categorized differently in every country. For example, the USFDA has benzodiazepines categorized as either D or X, meaning that there is potential harm to the unborn associated with benzodiazepines. Additionally, benzodiazepines have been associated with a greater risk of birth defects,[9] and infants born to mothers who used benzodiazepines may suffer complications after birth such as a withdrawal syndrome, floppy infant syndrome, seizures, among other problems. Pregnant mothers are encouraged to taper off of their benzodiazepine, and/or cross over to diazepam or chlordiazepoxide, as these benzodiazepines are associated with a less intense withdrawal syndrome.

Because benzodiazepines could be excreted in breastmilk, breast-feeding mothers who take benzodiazepines regularly should avoid breast-feeding. Discovering that one is pregnant while they’re on or tapering a benzodiazepine can be very stressful and traumatic, as the taper process may be faster than what the mother can really tolerate, and as mentioned above, her hormones may be already making her sick if she’s dependent on a benzodiazepine.

Some mothers experience a remission of symptoms during pregnancy; this could possibly be explained by high levels of progesterone and/or other GABAergic endogenous hormones, which rise during pregnancy and decrease sharply after childbirth, possibly contributing to post-partum health problems.

Parents of any gender are affected

Many parents have lost an unacceptable amount of quality time with their children as they grew up before their eyes, or, sometimes not even that. Some parents lose custody battles (during divorces which can also be a devastating effect of benzodiazepine withdrawal), as they become too disabled to care for their children, or spend the quality time with them that they would want. Some sufferers report that they feel fortunate if they have a parent, sibling or other such help in caring for their children until they recover; though many parents, especially single parents, do not have this luxury. Mothers and fathers alike report that they feel a sense of tremendous guilt because while many of their children do understand that their parent is unwell, the children may not even be aware of how it’s negatively impacting their growth and development.

From an anonymous sufferer of BWS:

My 13 y/o daughter and I used to do everything together. She was my buddy. I am now unable to do much with her anymore. It is in her best interest that I stay clear of her, because the way I look and act in withdraw is damaging to her. I only hope that I will get better and can preserve what we had before she gets too much older

Those who are experiencing this in the long-term and during their child-bearing and child-rearing years report to feel robbed of the choice to have children.

From an anonymous sufferer of BWS-PWS:

This happened to me during child-bearing years and has persisted so long, it’s probably removed any chance I had of being a parent. Which is hard to swallow.


Women Benzodiazepine Activists Speaking Out:

On January 24, 2017, inspired by Sonja Styblo, Christina Souza (pictured) and Lauren Omartian presented testimony on the toxicity of benzodiazepines to the Massachusetts Commission on the Status of Women. A writer and photographer from the Sentinel & Enterprise covered the hearing held at the Leominster Public Library.


FURTHER READING: Hormones and Benzodiazepines PMS, Postpartum Depression, Sedative Withdrawal Believed to Have Common Brain-Receptor Link