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Menopausal Symptoms

Mental Health

Low Sex Drive

Vaginal Symptoms

Sleep Disturbances

treatment options bioidentical hormone replacement therapy (BHRT)
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Bioidentical Hormones (BHRT)

Synthetic Hormones

Oral Preparations

Vaginal Creams

Skin Gels

Pellets

Bioidentical vs Synthetic Hormones?

What They Are

Bioidentical hormones are hormones that have the identical chemical structure as the hormones found in your body.  

Synthetic hormones have a different chemical structure than the hormones found in your body.  These chemical differences are often added to increase absorption or prevent premature metabolism (breakdown).

Bioidentical
Synthetic
BHRT vs synthetic hormones

What They Are Not

Bioidentical hormones are not "natural".  They are synthesized in a lab, same as synthetic hormones, from a precursor molecule.  That molecule is often "natural" in the sense that it is plant based.    

Bioidential vs Synthetic Hormones

This topic is passionately debated, with each side loyally defending their position.  

The following links are to reputable sources for health information and can be helpful in educating oneself of the differences between bioidentical hormones and synthetic hormones.  

Are Bioidentical Hormones Superior to Hormone Medications?

Harvard Health Publishing

Bioidentical Hormones: Are They Safer?

Mayo Clinic

Bioidential Hormones

Cleveland Clinic

 

Not many people realize that there are FDA approved bioidentical hormones including estradiol, progesterone, and DHEA.

I am impartial and do not join in the debate.  They both have pros and cons to their use.  I prefer to educate the individual and let them make an informed decision that they feel is best for their health.  

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Depression and female hormones

1) Han H, Xia X, Zheng H, Zhong Z, Zhao C, Wang X, Zhi X. Factors associated with the high susceptibility to depression of women during the perimenopause. Brain Behav. 2023 Jan;13(1):e2826. 2) Frokjaer VG. Pharmacological sex hormone manipulation as a risk model for depression. J Neurosci Res. 2020 Jul;98(7):1283-1292. 3) Gordon JL, Rubinow DR, Eisenlohr-Moul TA, Xia K, Schmidt PJ, Girdler SS. Efficacy of Transdermal Estradiol and Micronized Progesterone in the Prevention of Depressive Symptoms in the Menopause Transition: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Feb 1;75(2):149-157 4) Hernández-Hernández OT, Martínez-Mota L, Herrera-Pérez JJ, Jiménez-Rubio G. Role of Estradiol in the Expression of Genes Involved in Serotonin Neurotransmission: Implications for Female Depression. Curr Neuropharmacol. 2019;17(5):459-471. 5) Kolatorova L, et al. Progesterone: A Steroid with Wide Range of Effects in Physiology as Well as Human Medicine. Int J Mol Sci. 2022 Jul 20;23(14):7989.

The risk of major depressive disorder in women passing through menopause is twice that of women that are premenopausal.  This may be related to the vasomotor symptoms, irritability, and lack of sleep that is prevalent during menopause.  Scientist believe that this is a contributing factor for why the majority of divorces occur for women that are menopausal.

One study looked at rates of depression in menopausal women being treated with estrogen and progesterone compared to placebo.  Those being treated with hormones had half the rate of depression compared to their counterparts.

In addition to addressing menopausal symptoms, estrogen increases serotonin production and expression of serotonin receptors in the brain.  It also increased production of norepinephrine in the central nervous system.  Increasing these neurotransmitters is the purpose of selective serotonin reuptake inhibitors (SSRI) and serotonin and norepinephrine reuptake inhibitors (SNRI) anti-depressant drugs.

Progesterone exerts a mood stabilizing effect by activating GABA receptors in the brain, the same target as the drug gabapentin. 

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Sleep and progesterone

1) Kolatorova L, et al. Progesterone: A Steroid with Wide Range of Effects in Physiology as Well as Human Medicine. Int J Mol Sci. 2022 Jul 20;23(14):7989. 2) Nagy B, et al. Key to Life: Physiological Role and Clinical Implications of Progesterone. Int J Mol Sci. 2021 Oct 13;22(20):11039.

Progesterone is commonly prescribed orally and given at bedtime to help with hormone related sleep disturbances. 

Allopregnanolone, a product of progesterone metabolism, binds to the GABA receptors in the brain.  This results in a sedative, hypnotic, and anxiolytic effect.  In simpler terms, progesterone helps with calming, relaxation, and sleep.   

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Vaginal health and DHEA

1) Scavello I, et al. Sexual Health in Menopause. Medicina (Kaunas). 2019 Sep 2;55(9):559. 2) La Rosa VL, et al. Treatment of genitourinary syndrome of menopause: the potential effects of intravaginal ultralow-concentration oestriol and intravaginal dehydroepiandrosterone on quality of life and sexual function. Prz Menopauzalny. 2019 Jun;18(2):116-122. 3) Kagan R, et al. Practical Treatment Considerations in the Management of Genitourinary Syndrome of Menopause. Drugs Aging. 2019 Oct;36(10):897-908.

Dehydroepiandrosterone (DHEA) is a hormone closely related to testosterone. It is frequently applied topically to the vagina to address vaginal symptoms related to menopause and sexual dysfunction.  It has the following effects:

  • Reduces vaginal pH to premenopausal levels (decrease UTI's)

  • Improves vaginal epithelial thickness

  • Increases nerve density in the vagina

  • Improves the collagen and muscularis layer of vaginal tissue

  • Decreases vaginal dryness

  • Reduces vaginal irritation & itching

  • Reduces pain during intercourse

  • Improves sexual function (desire, arousal, lubrication, orgasm, satisfaction, reduces pain)

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Vaginal microbiome and estrogen

1) Joseph RJ, et al. Finding a Balance in the Vaginal Microbiome: How Do We Treat and Prevent the Occurrence of Bacterial Vaginosis? Antibiotics (Basel). 2021 Jun 15;10(6):719. 2) Auriemma RS, et al. The Vaginal Microbiome: A Long Urogenital Colonization Throughout Woman Life. Front Cell Infect Microbiol. 2021 Jul 6;11:686167. 3) Alperin M, et al. The mysteries of menopause and urogynecologic health: clinical and scientific gaps. Menopause. 2019 Jan;26(1):103-111. 4) Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. 1993 Sep 9;329(11):753-6.

The vaginal microbiome refers to the healthy bacteria that colonize the female reproductive system.  Lactobacillus spp. is the most common organism and is responsible for maintaining a proper vaginal pH.  This prevents yeast infections, UTI's, and bacterial vaginosis.  

Estrogen promotes a healthy vaginal epithelial mucosa and increased intracellular glycogen levels. Lactobacillus spp. grow well in the epithelial mucosa and use glycogen as fuel.  This promotes a large colony of healthy vaginal bacteria.

Decreased estrogen during menopause results in lower Lactobacillus spp. levels and subsequent growth of other microbes like Gardnerella vaginalis, Ureaplasma urealyticum, Candida albicans, Prevotella spp., E. coli, and Enterobacteriaceae. These microbes cause yeast infections, vaginosis, and UTI's.

Estrogen replacement restores the vaginal epithelial mucosa allowing for Lactobacillus spp. colonization and a reduced rate of vaginal and urinary tract infections.

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Vaginal health and estrogen

1) Scavello I, et al. Sexual Health in Menopause. Medicina (Kaunas). 2019 Sep 2;55(9):559. 2) Rahn DD, et al; Society of Gynecologic Surgeons Systematic Review Group. Vaginal estrogen for genitourinary syndrome of menopause: a systematic review. Obstet Gynecol. 2014 Dec;124(6):1147-1156.

Vaginal estrogen helps relieve the following urinary symptoms related to menopause:

  • Painful urination

  • Increased urge to urinate

  • Increased urinary frequency

  • Increased urination at nighttime 

  • Stress urinary incontinence

  • Urge urinary incontinence 

  • Increased frequency of urination


Vaginal estrogen helps sexual symptoms related to menopause in the following way:

  • Restores vaginal and urethral epithelial thickness

  • Maintains a healthy pH

  • Promotes a healthy vaginal microbiota 

  • Increases genital blood flow

  • Reduces dryness

  • Decreases pain during intercourse

  • Improves itching and burning

  • May improve sexual genital arousal and orgasmic function

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Systemic effects of estrogen

1) Manolagas, S. C., O'brien, C. A., & Almeida, M. (2013). The role of estrogen and androgen receptors in bone health and disease. Nature Reviews Endocrinology, 9(12), 699. 2) Iorga, A., Cunningham, C. M., Moazeni, S., Ruffenach, G., Umar, S., & Eghbali, M. (2017). The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy. Biology of sex differences, 8(1), 1-16. 3) Hwang WJ, Lee TY, Kim NS, Kwon JS. The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders. International Journal of Molecular Sciences. 2021; 22(1):373. 4) Cignarella, A., & Bolego, C. (2010). Mechanisms of estrogen protection in diabetes and metabolic disease. Hormone Molecular Biology and Clinical Investigation, 4(2), 575-580.

BONE

Estrogen helps prevent osteoporosis and promotes bone strength.

HEART

Estrogen appears to have a cardioprotective effect if started within 10 year of menopause.  If started after 10 years of menopause, it may have negative effects on the heart. 

BRAIN

Estrogen appears to have a protective effect against Alzheimer's disease by promoting synthesis of brain-derived neurotrophic factors (BDNF). This must be started during midlife to have this effect. If started after midlife it may increase the risk of dementia.

Estrogen helps promote proper mental health and reduced risk of depression.

ENDOCRINE

Estrogen lowers your risk of diabetes.

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Testosterone in women

1) Parish, S. J., Simon, J. A., Davis, S. R., Giraldi, A., Goldstein, I., Goldstein, S. W., ... & Vignozzi, L. (2021). International Society for the Study of Women’s Sexual Health clinical practice guideline for the use of systemic testosterone for hypoactive sexual desire disorder in women. The journal of sexual medicine, 18(5), 849-867. 2) Traish, A. M., Vignozzi, L., Simon, J. A., Goldstein, I., & Kim, N. N. (2018). Role of androgens in female genitourinary tissue structure and function: implications in the genitourinary syndrome of menopause. Sexual Medicine Reviews, 6(4), 558-571. 3) Kim, M. M., & Kreydin, E. I. (2018). The association of serum testosterone levels and urinary incontinence in women. The Journal of Urology, 199(2), 522-527. 4) Chen, Yingxiu, Xin Song, Weilin Fang, Tingting Lv, Jin Huang, Zhikang Cai, and Jianwei Lv. "Correlation of serum circulating testosterone levels with stress urinary incontinence in postmenopausal women." World Journal of Urology (2023): 1-6. 5) Hristov, K. L., Parajuli, S. P., Provence, A., & Petkov, G. V. (2016). Testosterone decreases urinary bladder smooth muscle excitability via novel signaling mechanism involving direct activation of the BK channels. American Journal of Physiology-Renal Physiology, 311(6), F1253-F1259.

Testosterone receptors are found throughout genitourinary tissues, such as the vagina, clitoris, labia, vestibule, bladder, and supporting structures of the pelvic floor. They are also found in the areas of the brain related to motivation and reward. 

 

Therefore, testosterone exerts an effect in three main areas of female physiology.  Sexual function, urinary function, and sexual drive or libido.


Sexual Funciton

  • Reduces vaginal pH to premenopausal levels (decrease UTI's)

  • Improves vaginal epithelial thickness

  • Increases nerve density in the vagina

  • Improves the collagen and muscularis layer of vaginal tissue

  • Decreases vaginal dryness

  • Reduces vaginal irritation & itching

  • Reduces pain during intercourse

  • Improves sexual function (desire, arousal, lubrication, orgasm, satisfaction, reduces pain)

Urinary Function

  • Maintains muscle integrity of pelvic floor which supports the urethra and maintains continence 

  • Decreases bladder wall excitability (reduces urgency symptoms)

Libido

  • Improves desire for sex or sexual drive​

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Risk of hormone replacement therapy

1) Manyonda, I., Talaulikar, V. S., Pirhadi, R., Ward, J., Banerjee, D., & Onwude, J. (2022). Could perimenopausal estrogen prevent breast cancer? Exploring the differential effects of estrogen-only versus combined hormone replacement therapy. Journal of Clinical Medicine Research, 14(1), 1. 2) Hou, N., Hong, S., Wang, W., Olopade, O. I., Dignam, J. J., & Huo, D. (2013). Hormone replacement therapy and breast cancer: heterogeneous risks by race, weight, and breast density. Journal of the National Cancer Institute, 10)(18), 1365-1372. 3) Bergendal, A., Kieler, H., Sundström, A., Hirschberg, A. L., & Kocoska-Maras, L. (2016). Risk of venous thromboembolism associated with local and systemic use of hormone therapy in peri-and postmenopausal women and in relation to type and route of administration. Menopause, 23(6), 593-599. 4) Cirillo, D. J., Wallace, R. B., Rodabough, R. J., Greenland, P., LaCroix, A. Z., Limacher, M. C., & Larson, J. C. (2005). Effect of estrogen therapy on gallbladder disease. Jama, 293(3), 330-339.

Hormone replacement therapy is quite safe when done responsibly and at normal physiologic levels.  Like all medical therapies, it is not without the risk of side effects.  One must compare the risks and benefits of hormone replacement therapy to determine if it is right for you. 

Estrogen and progesterone may increase the risk of breast cancer.   Conversely, in some women, estrogen may lower the risk of breast cancer.1  This is highly variable so individual risk factors must be assessed.2 Regular mammograms should be performed while on hormone replacement therapy.  

Estrogen can increase the risk of clot formation.  However, this effect is only seen with oral estrogen, not vaginal or topical estrogens.2 

Estrogen will increase the risk of uterine cancer if not used in conjunction with progesterone.  There is no risk of uterine cancer if you have had a hysterectomy. 

Estrogen increases the risk of gallbladder inflammation and gall stones.3

As mentioned previously, there is an age dependent effect of estrogen on increased risk of cardiovascular disease and dementia.  This effect is not seen if estrogen is started early during perimenopause. 

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