Testosterone Production in Women
Testosterone is produced in the ovaries, adrenal gland, and through peripheral conversion from circulating androgens. Testosterone levels in women decline significantly with age.
By age 40, most women have lost about ½ the testosterone they had when they were 20.
Ovaries continue to make T even after Estrogen production stops
Testosterone production from adrenal glands declines with aging, but continues post-menopause.
Women with bilateral salpingo oophorectomy (BSO) have 50% further decline.
References:
Glaser R. York A.E. Dimitrakakis C. Beneficial effects of testosterone therapy in women measured by the validated Menopause Rating Scale (MRS). Maturitas. 2011; 68: 355-361
Glaser, R., Kalantaridou, S., & Dimitrakakis, C. (2013). Testosterone implants in women: pharmacological dosing for a physiologic effect. Maturitas, 74(2), 179–184
The Facts About Testosterone
Between ages 20 and 40, women can lose 50% of their testosterone production
Between ages 30-70, men can lose 1-3% of total testosterone production per year
As humans age, a significant change occurs in the balance of albumin and SHBG. Albumin is a protein found in the body that binds to and transports testosterone. Sex-Hormone Binding Globulin (SHBG) is a protein that binds to, transports and inhibits the function of testosterone. SHBG controls the amount of testosterone an individual's body tissues can use.
References:
Tetsuo Hayashi & Takumi Yamada (2008) Association of bioavailable estradiol levels and testosterone levels with serum albumin levels in elderly men, The Aging Male, 11:2, 63-70, DOI: 10.1080/13685530701779234
History of Testosterone Use in Women
Testosterone has been used as far back as 1937 to treat symptoms of menopause in women. The first T pellet was developed by Robert Benjamin Greenblatt in 1949, and was originally intended for women with “gynecologic disorders”. While the use of Testosterone for women is limited in the US, testosterone is licensed and has been used to treat women for the past 60 years in Australia and England.
References:
Rebecca Glaser, Constantine Dimitrakakis,Testosterone therapy in women: Myths and misconceptions, Maturitas, Volume 74, Issue 3, 2013, Pages 230-234, ISSN 0378-5122, https://doi.org/10.1016/j.maturitas.2013.01.003
Testosterone Method of Delivery
(and Why it Matters)
ORAL:
Requires daily administration.
First-pass effect (pharmacological phenomenon in which a medication undergoes metabolism at a specific location in the body and decreases the active drug's concentration upon reaching systemic circulation or its site of action)
May cause GI upset or nausea.
Not as effective as other methods.
Methyltestosterone can sometimes cause hepatotoxicity, for instance elevated liver enzymes, cholestatic jaundice, peliosis hepatis, hepatomas, and hepatocellular carcinoma, with extended use.
With buccal/sublingual forms, must be dosed 3x per day.
TRANSDERMAL:
Requires daily or twice daily administration.
Avoids first-pass metabolism by the liver.
Can cause skin irritation
Some individuals are unable to properly absorb.
Blood levels will vary.
Possible transfer to others through skin-to-skin contact.
INJECTABLE:
Weekly or biweekly administration.
Inconsistent, fluctuating levels, creating a “roller coaster” effect.
Hormone level rapidly increases.
Injection causes some pain.
Some individuals may have allergic reaction to carrier oils
PELLET:
Administered every 3 or 4 months based on gender.
Provide steady, stable hormone levels over time.
Minimal time and discomfort associated with insertion.
Extremely low level of pellet extrusion.
Most patients return to normal activities minutes after treatment.
Dose adjustments are made by assessing response and follow up blood work.
References:
Čeponis, J., Yadav, P., Swerdloff, R.S., Wang, C. (2017). Testosterone Therapy: Transdermal Androgens. In: Hohl, A. (eds) Testosterone. Springer, Cham. https://doi.org/10.1007/978-3-319-46086-4_11
Testosterone Pellets
Multiple and customized dosing options.
Consistent, steady levels.
Predictable absorption.
Pellets kick in at about a week.
Patient stops other forms of Testosterone at one week.
Rise and peak around weeks 4-6.
Reduced risk of platelet aggregation.
Convenient option with fewer office visits for maximized patient satisfaction and compliance.
1-4 times per year for women.
1-3 times per year for men.
References:
1497 A MULTI-INSTITUTIONAL OBSERVATIONAL STUDY ON TESTOSTERONE LEVELS AFTER TESTOSTERONE PELLET (TESTOPEL™) INSERTION
Andrew McCullough, Mohit Khera, Wayne Hellstron, Abraham Morgentaler, Larry Levine and Irwin Goldstein
Risks Associated with Low Testosterone in Women
Low Testosterone can increase the risk of certain conditions including the following:
Alzheimer's disease
Cardiovascular disease
Osteoporosis-related fractures
Breast cancer
Diabetes mellitus
Sarcopenia
References:
Donovitz GS. A Personal Prospective on Testosterone Therapy in Women-What We Know in 2022. J Pers Med. 2022 Jul 22;12(8):1194. doi: 10.3390/jpm12081194. PMID: 35893288; PMCID: PMC9331845
Testosterone and Women: International Expert Consensus Resolutions
Testosterone is not a male-exclusive hormone. It is the most abundant gonadal hormone throughout a woman’s life.
Serum testosterone levels do not correlate with symptoms of testosterone deficiency in women. Optimal ranges of serum testosterone levels in women have not been established.
Female testosterone insufficiency is a clinical syndrome that may occur during any decade of adult life.
Testosterone therapy may be breast protective.
Testosterone insufficiency in women negatively affects sexuality, general health and quality of life. Testosterone supplementation may positively influence sexuality, general health and quality of life.
Testosterone insufficiency may be associated with an increased risk of cardiovascular disease in women.
Testosterone optimization may be brain protective and may enhance cognitive function.
Testosterone optimization may be a key component for improved bone health.
Testosterone therapy in women has no adverse effects on lipids and/or cardiovascular risk.
Studies of testosterone supplementation show benefits exceed the risk and consistent purity and potency can be achieved.
References:
Gary Donovitz, MD (Chairman), Erika Schwartz, MD, Charles Miller, MD Mickey Barber, MD, Florence Comite, MD, Ken Janson, MD, Jeffrey Leake, MD, Edwin Lee, MD, Jeffry Life, MD, Luis Martinez, MD, Douglas Woodford, MD “Testosterone Insufficiency and Treatment in Women: International Expert Consensus Resolutions”
Signs and Symptoms of Testosterone Deficiency
Common symptoms of testosterone deficiency include the following:
Insomnia
Depression
Headaches
Worsening of quality of life (mood, affect, energy)
Vaginal vasocongestion
Reduced sex drive and enjoyment
Reduction of pubic hair, bone mass and muscle mass
Benefits of TRT in Women
Benefits often experienced by women who receive Testosterone Replacement Therapy include the following:
Better sleep
Reduced "brain fog"
Enhanced cognitive function
Increased energy and sense of well being
Fight effects of osteoporosis
Stronger bones and skeletal growth
Lower cholesterol
Heart protection
Enhanced libido and sexual function
References:
Clarke BL, Khosla S. Androgens and bone. Steroids. 2009 Mar;74(3):296-305. doi: 10.1016/j.steroids.2008.10.003. Epub 2008 Oct 17. PMID: 18992761; PMCID: PMC2679948.
Deborah R Cameron, Glenn D Braunstein, Androgen replacement therapy in women, Fertility and Sterility, Volume 82, Issue 2, 2004, Pages 273-289, ISSN 0015-0282
The Effect of Testosterone Pellets on Bones
Testosterone builds and maintains bones.
Effective for prevention and treatment of osteoporosis.
In postmenopausal women, treatment with combined estradiol and testosterone implants is more effective than estradiol implants alone.
References:
Zhang H, Ma K, Li RM, Li JN, Gao SF, Ma LN. Association between testosterone levels and bone mineral density in females aged 40-60 years from NHANES 2011-2016. Sci Rep. 2022;12(1):16426. Published 2022 Sep 30. doi:10.1038/s41598-022-21008-7
Davis SR, McCloud P, Strauss BJ, Burger H. Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality. Maturitas. 1995;21(3):227-236. doi:10.1016/0378-5122(94)00898-h
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