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Can Oral Estrogen and Testosterone Improve a Woman's Sex Drive?

A postmenopausal woman is seeking treatment for her decreased menopause-related sexual desire.

Question:

A 53-year-old postmenopausal woman presents as a new patient consult and for a second opinion. She underwent natural menopause at age 52 and had been on oral Hormone Therapy for severe hot flashes symptoms. She complains of decreased libido and has read about oral estrogen plus testosterone as an option to improve her sex drive and her continued hot flashes. One of her friends is also on estrogen/testosterone hormone therapy and shared noticeable improvement in libido. The patient and her husband have tried sexual counseling with minimal improvement. She has no interest in stopping estrogen/progestin therapy currently because when she attempted to stop 3 months ago, her menopause symptoms returned. She has well-controlled hypertension and is otherwise healthy, with a body mass index of 26 kg/m2 and normal lipid profile and liver-function tests. Her current gynecologist does not recommend adding testosterone therapy, and she is seeking a second opinion. How would you proceed with counseling and treating her menopause-related sexual desire complaints?

Answer:

Answer by Holly L. Thacker, MD, FACP, CCD, NCMP

Based on the case description, this woman has already been diagnosed with postmenopausal Hypoactive Sexual Desire Disorder (HSDD). Before prescribing her off label testosterone, I would taking the following steps:

  1. Ask androgen sensitivity questions such as abnormal hair growth, androgenic hair patterned hair thinning, acne, oily skin and conversely query for any hints of androgen deficiency including oophorectomy history, prolonged glucorticoid use, loss of muscle mass, and/or otherwise unexplained fatigue.
  2. In midlife women, I am also interested in her obstetrical history including gestational diabetes which increases risk of OSAS which in turn can contribute to female sexual dysfunction.
  3. A review of all medications, supplements and lifestyle are in order.
  4. A physical exam and assessment of pelvic floor function and any possible contributions of undiagnosed genito-urinary syndrome of menopause is in order.

One of my mentors, friends and a true giant in the menopause field Dr. Phil Sarrel (who leads the non-profit I participate with - Advancing Health After Hysterectomy) and colleagues have reported on sexual behavior with estrogen–androgen therapy in postmenopausal women dissatisfied with estrogen only therapy.(1) I would not summarily dismiss prescribing this simply because it is “not FDA-approved” and is unlikely to ever be FDA-approved. In this COVID-19 age, the general public is quickly becoming acquainted with the fact that we physicians frequently prescribe “off label” therapies for several good reasons.

As an aside, I will never forget meeting the great Dr. Sarrel in 1996 at the NAMS meeting in Chicago where my poster on migraine headache in women on double blind cross over trial of weekly transdermal EP patch vs oral HT did not show that the patch was better as I had hypothesized.(2) He aptly noted, “Everyone knows the weekly patch estradiol levels drop by day 7.” Everyone except for apparently me at that time! Dr. Sarrel has eloquently discussed the psychosexual effects of menopause and the role for androgen therapy.(3)

Clinically, changing from oral estrogen alone to estrogen-testosterone can be helpful in refractory hot flashes as well as in suspected androgen deficiency. The Fertility and Sterility "Princeton Consensus Conference on Androgens" is a very valuable resource.(4) Consideration of changing from oral HT to transdermal HT may help boost free testosterone levels by reducing Sex Hormone Binding Globulin (SHBG).(5)

There are at least three clinical situations in which oral esterified estrogen/methyltestosterone makes a difference mostly explained by lowering SHBG being superior to estrogen alone:

  1. Failure of systemic estrogen therapy to control vasomotor symptoms.
  2. Failure of standard hormone therapy to restore sexual desire.
  3. Failure of standard hormone therapy to stop bone loss. Older women who are post oophorectomy tend to have the lowest free testosterone levels.

In this lady, after discussion of all risks/benefits/alternatives I would consider changing her regimen to esterified estrogens/methyltestosterone HS (half strength) with adequate progestin (for endometrial protection) and re-assess in 3 months. Alternatively, off label topical testosterone applied to clitoris/vulva with either transdermal EP therapy or oral EP therapy could be considered with the need to assess total and free testosterone levels in 3 months.(6)

Unfortunately, many insurance companies will not cover EEMTHS which is available generically and in this situation women can purchase via the cash price the full strength EEMT and cut it in half. This is generally affordable and/or one can pay out of pocket for compounded testosterone in a Vera base ointment formulation which is generally also affordable. The absolute cheapest alternative for women with THBSO is oral estradiol twice daily with oral over the counter DHEA which via liver is aromatized to estradiol and testosterone. Of course, any woman with an endometrium needs progestin opposition.

Clinically, I have safely prescribed oral estrogen-androgen therapy for 3 decades. The combination of the bureaucracy of the federal government, insurance companies, prior authorizations, the electronic medical record, as well as Pharmacy Benefit Managers who control formularies and physicians’ prescribing practices will not dissuade me from appropriately treating my postmenopausal patients in whom sexual health is important.

References

  1. Sarrel PM, Dobay B, Wiita B. Sexual behaviour and neuroendocrine response in estrogen and estrogen‑androgen replacement in postmenopausal women dissatisfied with estrogen‑only therapy. Journal Reproductive Medicine. 1998;43:847-856.
  2. Thacker HL, Booher DL, Solomon GD, Kunkel, RS. “Migraine Headaches in Postmenopausal Women on Hormone Replacement Therapy.” North American Menopause Society Annual Meeting. Chicago, IL. September 26, 1996. Menopause 1996; 3:239-40.
  3. Sarrel PM. Psychosexual effects of the menopause: Role of androgens. Am J Obstet Gynecol. 1999;180:S319‑324.
  4. Bachmann G, Bancroft J, Braunstein G et al. Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment. Fertil Steril 2002;77:660-665.
  5. Sarrel PM. Androgen deficiency: menopause and estrogen-related factors. Fertil Steril 2002;77 (Suppl4):S63-67.
  6. Davis SR, Baber R, Panay N et al Global Consensus position statement on the Use of Testosterone Therapy for Women. J Clin Endo and Metab vol 104 (10) 2019; 4660-4665.