1. The Postpartum Hormonal Rollercoaster
After the arrival of a new baby, a parent’s body undergoes significant hormonal shifts. Let’s break it down:
hCG (Human Chorionic Gonadotropin): During the first 48 hours after delivery, hCG levels drop. This hormone, which played a crucial role during pregnancy, starts to decline as the placenta is no longer producing it.
Estrogen and Progesterone: These hormones, which surged during pregnancy, also plummet postpartum. Estrogen, in particular, has a profound impact on mood, energy levels, and overall well-being.
Oxytocin: Often called the “bonding hormone,” oxytocin remains essential. It facilitates uterine contractions during labor and helps with milk ejection during breastfeeding.
Prolactin: This hormone kicks into high gear to support milk production. Breastfeeding parents typically have slightly elevated prolactin levels for several months.
Cortisol: The stress hormone gradually declines postpartum, but it can remain elevated if stress levels persist.
2. Postpartum Depression
Postpartum depression (PPD) is a disabling condition that affects at least 5% of birthing parents worldwide. With it comes extreme lethargy and sadness following birth that significantly impairs one's functioning. Although "baby blues" occur after 4 out of 5 births, PPD is more severe and persistent than this common malady (1).
First-line treatments include psychotherapies such as cognitive behavior therapy and interpersonal therapy, as well as SSRI antidepressants. Fluvoxamine, paroxetine, and sertraline are preferred in breastfeeding/chestfeeding patients due to minimal circulating levels found in breastfed infants (1).
One small study found significant improvements in postpartum depression and anxiety with prenatal hypnosis as a prevention, and more study in this area is needed (2).
Because timely psychotherapy may be inaccessible in the weeks following birth, and because antidepressants may cause undesirable side effects, there is an intense interest in other potential therapies for PPD.
3. Systemic Hormone Therapy
Estrogen
Systemic estrogen therapy increases estrogen in the bloodstream to a normal level. In the immediate postpartum period, estrogen levels plummet to those seen after menopause, which brings to question whether menopausal hormone therapy (MHT) may be appropriate.
MHT has not historically been used to treat postpartum symptoms, in part because symptoms are often self-limited, and also due to concerns for milk supply. Severe PPD, however, is one circumstance where a trial of MHT may be warranted.
In 2008, a Cochrane review of this method summarized: "Oestrogen therapy may be of modest value for the treatment of severe postpartum depression (3)."
There is also some evidence that estradiol can be used preventatively for PPD.
In one case study, a woman with premature ovarian insufficiency due to Turner syndrome experienced severe postpartum depression that required electroconvulsant therapy. For her second pregnancy, MHT was started preemptively at birth and she did not experience any clinically significant mood disturbances (4).
More research is needed prior to reaching conclusions, including safety trials in breastfeeding/chestfeeding patients. Although studies of high estradiol levels in mouse mothers have found adverse growth in mouse pups, this result has not been replicated in humans. One small study found that natural estradiol levels in human milk were positively correlated with infant growth, while progesterone levels were negatively correlated with infant growth (5,6). Therefore, administration of MHT must be carefully considered.
A "conceptual update" written in August 2024 finds that PPD can be predicted by epigenetic alterations in estrogen-responsive genes, yet finds no effective estrogen-based therapies to date (7).
Progesterone
The Cochrane review cited above discussed uncontrolled studies from the 1980s showing benefits of bio-identical progesterone used preventatively for PPD, but warned against the use of synthetic progestins, which were found to make mood worse (3).
Two neuroactive steroid medications, brexanolone and zuranolone, are analogs of a progesterone metabolite named allopregnanolone. These act on the GABA receptors in the brain and have been FDA approved to treat PPD as of 2023.
Of note, treatment with MHT can create a separate set of issues. Typical doses may cause breast tenderness, vaginal bleeding, bloating, and headaches. Implications of MHT on milk production and infant outcomes have not been studied.
4. Oxytocin: The Bonding Hormone
Oxytocin, the so-called "bonding hormone" that is released during birth and breastfeeding, has been implicated in the development of postpartum depression.
A 2020 systemic review found that higher natural levels of oxytocin in the blood are associated with lower levels of PPD. However, the authors report that no conclusions can be drawn about synthetic oxytocin administration as a treatment for PPD (8).
A 2023 systematic review looked at six randomized controlled trials of oxytocin for PPD. One trial showed an improvement in PPD, two showed no effect, and one showed worsening PPD. On the flipside, administration of oxytocin consistently improved the mother's cognition and subjective relationship with her infant (9).
Interestingly, one small study found that the administration of oxytocin (Pitocin) during and after delivery was associated with a significantly higher quality of observed mother-infant bonding, when controlling for sleep quality (10). However, there is also some evidence that oxytocin administration during labor may negatively impact the infant's sucking reflex in the hours after birth (11).
Oxytocin and Breastfeeding
Oxytocin administration has not been clearly shown to improve milk production or to relieve breast engorgement (11).
5. Local Estrogen Therapy
Local estrogen therapy targets specific areas, such as the vagina and vulva.
Vaginal Atrophy: Postpartum hormonal changes can lead to vaginal dryness, itching, and discomfort. Local estrogen can help restore tissue health.
Safety: Local estrogen has minimal systemic effects, making it a preferred choice for some individuals. There are no known complications in breastfeeding, and overall vaginal estrogen is considered safe in postpartum use (12). However, more research is needed regarding its effectiveness in the postpartum period, and some clinicians have found that dosing more than twice a week may impact milk supply.
Options:
Vaginal Creams: Micronized estradiol creams (like Estrace) are applied directly to the vaginal tissues. These can be used externally as well, which may help with healing of the perineum after delivery.
Vaginal Rings: Estring releases estrogen over 3 months, but may not be preferred due to higher estrogen exposure.
Vaginal Tablets: Vagifem provides a convenient tablet form.
Conclusion
Postpartum depression (PPD) is a significant and debilitating condition that affects a substantial number of birthing parents globally. While first-line treatments such as cognitive behavior therapy, interpersonal therapy, and SSRI antidepressants are effective, they may not be accessible or suitable for everyone.
The exploration of alternative therapies, including prenatal hypnosis, systemic hormone therapy, and the use of neuroactive steroids like brexanolone and zuranolone, offers promising avenues for treatment. However, these therapies come with their own set of challenges and potential side effects, necessitating further research and safety trials, especially for breastfeeding patients.
Additionally, while oxytocin has shown some potential in improving mother-infant bonding, its efficacy in treating PPD remains inconclusive.
Local estrogen therapy presents a safe option for addressing postpartum vaginal atrophy, but its effectiveness in the postpartum period requires more investigation.
Overall, a multifaceted approach that includes timely access to psychotherapy, medication management, and consideration of emerging therapies is essential for effectively managing PPD and improving the quality of life for affected individuals.
Disclaimer: This blog post is for informational purposes only. Always seek professional advice tailored to your unique situation.
Sources:
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Beevi Z, Low WY, Hassan J. The Effectiveness of Hypnosis Intervention in Alleviating Postpartum Psychological Symptoms. Am J Clin Hypn. 2019 Apr;61(4):409-425. doi: 10.1080/00029157.2018.1538870. PMID: 31017553.
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Shea AK, Wolfman W. The role of hormone therapy in the management of severe postpartum depression in patients with Turner syndrome. Menopause. 2017 Nov;24(11):1309-1312. doi: 10.1097/GME.0000000000000915. PMID: 28609392.
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Thul TA, Corwin EJ, Carlson NS, Brennan PA, Young LJ. Oxytocin and postpartum depression: A systematic review. Psychoneuroendocrinology. 2020 Oct;120:104793. doi: 10.1016/j.psyneuen.2020.104793. Epub 2020 Jul 6. PMID: 32683141; PMCID: PMC7526479.
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