Efficacy and Safety of Oral DHEA Therapy for Postmenopausal Women on Sexual Function, Wellbeing and Vasomotor Symptoms
Condition: Quality of Life; Menopausal Syndrome; Libido Disorder
Study type: Interventional
Phase: Phase 3

Summary: 
      This study is designed to evaluate the efficacy and safety of oral Dehydroepiandrosterone
      (DHEA) 50mg daily, for 12 months in naturally menopausal women with low libido who are not
      receiving systemic oestrogen or oestrogen- progestin therapy.

      Efficacy measures for the present study are effects on sexual function, wellbeing and
      menopausal symptoms. Safety measures will include endometrial assessment by transvaginal
      ultrasound (TVU), vital signs, lipid profiles, general electrolytes, effects on glucose
      metabolism and reports of adverse events.
    

Detailed description: 
      Dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) are the most abundant sex steroids in
      women. Dehydroepiandrosterone sulphate (DHEAS), a unique secretory product of the adrenal
      gland, and DHEA are converted at various sites in the body, such as the brain, bone and
      adipose tissue to estrogen or testosterone and their various by-products. DHEAS and DHEA
      levels decline with age and there has been considerable conjecture that this results in a
      loss of well-being and libido. DHEA is available as an over-the-counter nutritional
      supplement in the United States, and is being increasingly prescribed and formulated by
      compounding pharmacies across Australia. However, there is a paucity of data regarding the
      effects of oral DHEA on the well-being, sexual function and safety in women. Previous studies
      evaluating the effects of DHEA on either postmenopausal women or women with adrenal
      deficiency (Addison's disease) have produced conflicting results, with some studies finding
      benefit in terms of sexual function and well-being while other studies have found no benefit.
      Therefore, there is a need for an appropriately powered randomized controlled trial of the
      effects of DHEA therapy on sexual function and well-being in postmenopausal women. In
      addition, as DHEA may be metabolized to estrogens, whether DHEA will alleviate vasomotor
      symptoms merits evaluation. The effects of DHEA on the endometrial (uterine) lining requires
      assessment, given its potential to be converted to estrogen.

      The primary aim of the current study will be to assess the effects of DHEA therapy in
      naturally menopausal women on sexual function using the Sabbatsberg Self-Rating Scale (SSS)
      over 12 months in a randomized placebo controlled trial. In addition the effects on
      well-being will be assessed by the Psychological General Well-Being (PGWB) Index and
      menopausal symptoms will be evaluated by the Menopause Quality of Life (MENQOL) Intervention
      Questionnaire. A diary record will also be employed to assess the effects on sexual function.
      Safety will be assessed over the entire study. Participants will also undergo a transvaginal
      ultrasound (TVU) at the beginning and end of the study, to determine whether DHEA affects the
      endometrial lining.

      This randomized, double-blind, placebo-controlled study will be conducted in 240 women over a
      52-week period. Women will be randomized to receive either placebo or DHEA (50 mg/day) for a
      52-week period. It is anticipated that the study will require a 6-month recruitment period.
      The study duration will be approximately 56 weeks, with a 4-week screening period and
      treatment period of 52 weeks. The study will be conducted over approximately 13 months. This
      is a single-centre study and will be conducted at the Alfred Hospital.

      Potential participants will be generally healthy women aged 40 - 65 years who have undergone
      a natural menopause and are in a stable monogamous sexual relationship and not using hormone
      therapy (HT).

      Participants are required to attend 6 clinic visits over a blinded treatment period of 52
      weeks. Informed consent will be obtained from the participant prior to the commencement of
      any study procedure at the first clinic visit. If participants are eligible, they will be
      asked to return at the end of the screening period to be randomized and commence treatment.
      During the treatment period, participants will take one capsule daily (placebo or DHEA 50
      mg). All participants will return to the clinic 5 more times, at weeks 0, 12, 26, 38 and 52
      for assessments of efficacy and safety. Blood tests will be collected at Weeks -4, 0, 12, 26
      and 52 to assess safety and hormone levels. Prior to commencing the study, participants will
      require a mammogram if this has not been done within 12 months of study entry. A transvaginal
      ultrasound will be performed to assess endometrial thickness prior to commencement of the
      trial. A Papanicolaou smear will also be performed if the cervix is still present, in those
      women where a Pap smear has not been done within 12 months of screening. These
      investigations, except the mammogram and Pap smear, will be repeated at the completion of the
      study. All participants will have a complete physical examination which will include an
      assessment of vital signs, breast examination, and internal and external pelvic examination
      to assess for clitoromegaly (clitoral enlargement). Skin evaluations for scalp hair loss,
      hirsutism and acne, and assessment for voice changes will be made throughout the study.
      Participants will be required to complete various questionnaires to assess sexual function
      (SSS), menopausal symptoms (MENQUOL Intervention) and general well-being (PGWB) at Weeks 0,
      12, 26 and 52. Participants will also record satisfactory sexual events in a 28 day diary
      which will be done in the 4 weeks prior to Weeks 0, 12, 26 and 52.
    

Intervention name(s): dehydroepiandrosterone; placebo
Intervention type(s): Drug; Drug
Intervention description(s): dehydroepiandrosterone capsules 50.0 mg /capsule DHEA 248.5 mg /capsule Microcrystalline Cellulose, NF 1.5 mg /capsule Magnesium Stearate, NF in a 60 mg Capsule; Placebo capsules of 298.5 mg /capsule Microcrystalline Cellulose, NF 1.5 mg /capsule Magnesium Stearate, NF in a 60 mg Capsule manufactured to mimic the active DHEA capsule
Other intervention name(s): DHEA
Intervention MeSH terms: Dehydroepiandrosterone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: low libido; lack of wellbeing