Evaluation of Efficacy and Safety of Oral DHEA Therapy for Postmenopausal Women on Sexual Function, Wellbeing and Vasomotor Symptoms

Inclusion Criteria:

Women will be screened for study participation according to the following inclusion criteria at Visit 1 (Week -4). Generally healthy women must meet the following eligibility criteria:

1. Be 40 to 65 years of age and at least 12 months postmenopausal (no spontaneous menses in the last 12 months, or be over the age of 55 years, or hysterectomy with one or both ovaries in situ and follicle-stimulating hormone [FSH] > 20 IU/L. (An FSH > 20 IU/L will also be used to confirm menopausal status in non-hysterectomised women < 55 years, where menopausal status is unclear.)
2. Be sexually active - defined as being involved in any form of sexual activity at least once a month. Women do not require a partner.
3. Body mass index (BMI) 18-34 kg/m2.

4. Women will need to answer affirmatively to the following questions:

   • In previous years did you find sexual activity satisfying?
   • Do you feel that you have experienced a significant decrease in your desire or interest?
   • Would you like an improvement in your desire or interest for sexual activity?
   • Would you like to be treated for this?
5. Have a clinically acceptable screening bilateral mammogram. Having documented normal results on a previous mammogram within 12 months prior to Week -4 is acceptable.
6. Have ≤ 4 mm endometrial double thickness and no other abnormal findings on TVU if not hysterectomised.
7. Have a clinically acceptable Pap smear (no evidence of malignancy or squamous intraepithelial lesions) if the cervix is present, within 12 months of Week -4; otherwise, a Pap smear will be done at Week -4.
8. Be able and willing to participate in the study as evidenced by providing written informed consent.
9. Baseline DHEAS level of < 2.1 umol/L (lowest 10th centile for women less than 45)

Exclusion Criteria:

1. Have a BMI < 18 or > 34 kg/m2
2. Dyspareunia not alleviated by use of lubricants.
3. Severe depression (Beck Depression Inventory Score-II [BDI] > 20).

4. Have partnership problems or poor feeling for partner. This will be established by interview by asking the following questions if a woman is in a specific relationship:

   1. Are you satisfied with your partner as a friend?
   2. Do you have concerns about your relationship?
5. Have used recent androgen therapy (testosterone implant within the last 28 weeks, transdermal testosterone cream within the last 8 weeks, tibolone within the last 12 weeks, oral testosterone within the last 4 weeks and injected testosterone within the last 6 weeks).
6. Have used treatment for depression (antidepressants, antipsychotics, antiepileptics) within 2 months prior to Week - 4 (Visit 1).
7. Have known severe psychiatric illness.
8. Have used estrogen, including vaginal conjugated equine estrogen, vaginal ring delivering up to 7.5 µg/day, or estrogen-progestin combinations in the last 2 months. (Use of Ovestin or Vagifem pessaries or cream will be allowed.)
9. Used phytoestrogens within 1 week prior to Week -4 (Visit 1). (Women will be allowed to participate in this trial, provided they cease using phytoestrogens for at least 1 week before visit 1.)
10. Have renal disease, liver disease, epilepsy or any other major illness that has occurred within the last 6 months.
11. Therapies known to induce liver enzyme metabolism or alter the metabolism of DHEA e.g. antiepileptics, dexamethasone, or antituberculous drugs.
12. Undiagnosed genital bleeding.
13. Have moderate to severe acne or hirsutism, have used antiandrogen therapy for acne or hirsutism in the preceding 5 years, or have androgenic alopecia.
14. Active malignancy or treatment for malignancy in the preceding 5 years (excluding non-melanotic skin cancer).
15. Report alcohol consumption > 3 standard drinks per day.
16. Have diabetes mellitus.
17. Have a history of cerebrovascular disease, thromboembolic disorders, myocardial infarction or angina at anytime before study entry or thrombophlebitis within the last 5 years.
18. An abnormal thyroid-stimulating hormone (TSH) value at screening (however, participants with an abnormal TSH, but normal free T4 and free T3 and no clinical signs or symptoms of thyroid disease, with or without replacement treatment, may be admitted to the study).
19. Have abnormal liver function (LFTs) which, in the opinion of the investigator, is significant and/or an ALT or AST > 3 times the upper limit of normal or bilirubin > 2 times the upper limit of normal.
20. Have, in the opinion of the investigator, any clinically significant pre-treatment laboratory parameter, which the investigator feels would impact on the health and well-being of the woman's ability to participate in the study.