Definitions for the quality of the evidence (+OOO, ++OO, +++O, and ++++); the strength of the recommendation (1 or 2); and for the difference between a "recommendation" and a "suggestion" are provided at the end of the "Major Recommendations" field.
Diagnosis
The Task Force recommends against making a diagnosis of androgen deficiency in women at this time because there is neither a well-defined clinical syndrome nor normative data on testosterone or free testosterone levels in women across their lifespans that can be used to define the disorder (1 | +OOO).
Treatment
Although evidence exists for short-term efficacy of testosterone in selected populations, such as surgically menopausal women, the Task Force recommends against the generalized use of testosterone by women because the indications are inadequate and evidence of safety in long-term studies is lacking (1 | +OOO).
To formulate clinical recommendations, the task force would require additional data 1) defining conditions that, when not treated with androgens, have adverse health consequences to women; 2) defining clinical and laboratory parameters that distinguish those with these conditions; and 3) assessing the efficacy and long-term safety of androgen administration on outcomes that are important to women diagnosed with these conditions.
This necessary clinical research cannot occur until the biological, physiological, and psychological underpinnings of the role of androgens in women and candidate disorders are further elucidated. Thus, the task force makes the following recommendations to the clinical and research community.
Needed Assays
The Task Force recommends the development of sensitive and specific assays to measure testosterone and free testosterone in women across their lifespans (1 | +++O).
Needed Research
The Task Force recommends additional research in the following human model systems to define the clinical syndrome of androgen deficiency and to study the benefits and risks of androgen therapy (1 | +OOO):
- Surgical menopause is a condition in which the ovarian, but not adrenal androgen precursors are removed abruptly independent of age.
- Hypopituitarism, although uncommon, can be used to study the physiological replacement of both ovarian androgens and adrenal androgen precursors.
- Anorexia nervosa may be used as a model of androgen deficiency secondary to dysfunction of the hypothalamic-pituitary and adrenal axes.
- Primary adrenal insufficiency allows for the investigation of the loss of adrenal androgen precursors in the presence of intact ovarian androgen function.
- Ablation-replacement models in normal women using GnRH analogs to eliminate ovarian androgens, with or without suppression of adrenal androgen precursors, offer another way to assess the effects of androgen withdrawal and replacement.
- Subjects with complete androgen insensitivity syndrome offer a way to investigate target tissue effects which are dependent on the androgen receptor but are independent of aromatization.
- There are studies in patients with low weight and HIV and with natural aging; however, these systems are too complex to recommend as initial models to understand the potential therapeutic role of androgens in women.
The Task Force recommends additional investigation using rodent and primate models to further define the specific targets of androgen action (1 | +OOO).
The Task Force recommends additional research into the role of local androgen production, action, and metabolism in tissues (1 | +OOO).
The Task Force recommends further study of physiologic targets of androgen action (1 | +OOO) such as:
- Sexual dysfunction
- Cognition
- Mood
- Bone
- Cardiovascular function
- Body composition
- Muscle strength and function
The Task Force recommends the following endpoints be considered for safety and risk assessment in future studies (1 | +OOO):
- Appearance of or change in hirsutism, acne, male pattern balding, clitoromegaly, and deepening of the voice.
- Cardiovascular and metabolic evaluation, with and without estrogen replacement, should include fasting lipid profiles, vascular reactivity, markers of insulin sensitivity, and markers of inflammation.
- Effects on the breast, with or without estrogen replacement, should be measured. Breast biopsy studies with in vitro markers of cell proliferation and apoptosis should be considered.
- Alterations in the endometrium with and without estrogen coadministration
- Alterations in mood using validated instruments
Definitions:
Strength of Recommendations
1 - Indicates a strong recommendation and is associated with the phrase "The Task Force recommends."
2 - Denotes a weak recommendation and is associated with the phrase "The Task Force suggests."
Quality of the Evidence
+OOO Denotes very low quality evidence
++OO Denotes low quality evidence
+++O Denotes moderate quality evidence
++++ Denotes high quality evidence
