andro study in women

[wilson6]

Original Article

Effects of Oral Androstenedione Administration on Serum Testosterone and Estradiol Levels in Postmenopausal Women

Benjamin Z. Leder, Karen M. Leblanc, Christopher Longcope, Hang Lee, Don H. Catlin and Joel S. Finkelstein
Endocrine Unit (B.Z.L., K.M.L., J.S.F.), Department of Medicine, and Biostatistics Center (H.L.), Massachusetts General Hospital, Boston, Massachusetts 02114; Departments of Medicine and Obstetrics and Gynecology (C.L.), University of Massachusetts Medical School, Worcester, Massachusetts 01655; and Departments of Medicine and Molecular and Medical Pharmacology (D.H.C.), Olympic Analytical Laboratory, University of California at Los Angeles, Los Angeles, California 90025

Abstract

Androstenedione is a steroid hormone and an intermediate in the synthetic pathway of both testosterone and estradiol in men and women. It is available without prescription and taken with the expectation that it may have beneficial effects on strength, general well-being, libido, and quality of life. Although studies have shown that oral androstenedione increases serum testosterone and estradiol levels in men, the hormonal effects of androstenedione in postmenopausal women are unknown. We randomly assigned 30 healthy postmenopausal women to receive 0, 50, or 100 mg androstenedione as a single oral dose. After androstenedione administration, we made hourly measurements of serum androstenedione, estrone, estradiol, and testosterone concentrations during 12 h of frequent blood sampling. The mean change (±SD) in serum androstenedione area under the curve (AUC) was greater in both the 50-mg (79 ± 39%) and 100-mg dose groups (242 ± 184%) than in the control group (-29 ± 28%) (P < 0.0001 for controls vs. 50-mg group and controls vs. 100-mg group). The mean change in serum androstenedione AUC was also greater in the 100-mg than 50-mg dose group (P = 0.0026). The mean change in serum estrone AUC was greater in both the 50-mg (108 ± 72%) and 100-mg dose groups (116 ± 119%) than in the control group (-5 ± 19%), although the control vs. 100-mg group comparison did not quite meet statistical significance (P < 0.0001 for controls vs. 50-mg group, P = 0.0631 controls vs. 100-mg group). The mean change in serum estradiol AUC remained stable after supplementation in all groups without any between-group differences observed (-11 ± 17%, 2.8 ± 34%, -11 ± 27%, for the control, 50-mg, and 100-mg groups, respectively). The mean change in serum testosterone AUC was greater in both the 50-mg (185 ± 146%) and 100-mg dose groups (457 ± 601%) than in the control group (-27 ± 13%) (P < 0.0001 for controls vs. 50-mg group and for controls vs. 100-mg group). The mean change in testosterone AUC was also greater in the 100-mg dose group than 50-mg dose group (P = 0.0257). There was considerable individual variability in the changes of serum androstenedione, estrone, and testosterone levels in the treated groups with peak serum testosterone levels exceeding the upper limit of normal in 4 of 10 women in the 50-mg dose group and 6 of 10 in the 100-mg dose group. We concluded that the acute administration of both 50-mg and 100-mg of androstenedione increases serum testosterone and estrone levels, but not estradiol levels, in postmenopausal women. If these hormonal effects are sustained during long-term administration, regular use of this supplement by postmenopausal women could thus cause both beneficial and adverse effects.

 

[MS]

Hmmmmm. Once again it's a shame they didn't do a similar experiment in younger, normal women. On the face of it, increased estrone and testosterone without an increase in estradiol is characteristic of PCOS. I wouldn't be too quick to take this stuff if I were premenopausal without knowing a lot more about the potential side effects of screwing with your hormones like that.

Wilson6 (or anyone else), do you know what effect a dose of testosterone that would raise T levels to a similar level would have on estrone/estradiol levels in women? Have you read the entire article? I'm wondering if the increase in estrone would be enough to suppress endogenous production over the long term, or would it just be topping estrogen up (again I'm trying to extrapolate to premenopausal women)?

 

[KEL]

In the 7/1/02 edition of OB/GYN News there is a study on female "androgen insufficiency"._ The even better news is that this article does not give specific diagnostic criteria (other than "low" testosterone levels- in the lower 25th percentile) nor recommendations for treatments._

Here is the article...I do not have the data from the study.

Provides management algorithm
New Statement Defines Androgen Insufficiency
Betsy Bates
Los Angeles Bureau
LOS ANGELES — A newly published consensus statement on female androgen insufficiency offers a working definition of the condition and an algorithm for its management.
It also emphasizes an urgent need for development of a practical, affordable assay for assessment of bioavailable testosterone in women. “Current androgen assays are unsatisfactory primarily because of their lack of [either] sensitivity or reliability at the lower ranges of normal,” the document states (Fertil. Steril. 77[4]:660-65, 2002).
Dr. Irwin Goldstein, director of the Center for Sexual Medicine and professor of urology at Boston University, hailed the new guidelines as a “bible,” offering perspective on a topic that has long been underappreciated. His remarks came during a session on female sexuality at the annual meeting of the American College of Obstetricians and Gynecologists.
The panel that wrote the statement consisted of experts in the field from throughout the United States and Australia.
Panelist Dr. Goldstein said that the document may specifically spur interest among ob.gyns. in treating the 60 million women in America who have sexual dysfunction. To date, less than 5% of ob.gyns. have indicated an enthusiasm to get involved in the field, perhaps because it has been marked by a lack of good research to guide their practice.
“Historically, androgens have been identified with masculinity or male sexual function, which has undoubtedly contributed to a lack of recognition of androgen effects in women,” according to the consensus statement, which was written by 19 panelists who attended a conference in June 2001 at the Robert Wood Johnson Medical School in Piscataway, N.J.
“In fact,” the statement continued, “androgens are necessary not only for the development of reproductive function and hormonal homeostasis in women, but they also represent the immediate precursors for the biosynthesis of estrogen. Androgens affect sexual desire, bone density, muscle mass and strength, adipose tissue distribution, mood, energy, and psychological well-being.”
To help guide clinicians, the panel defined androgen insufficiency in women as a pattern of clinical symptoms in the presence of decreased bioavailable testosterone and normal estrogen status.
Symptoms must be present for a diagnosis to be made and can include a diminished sense of well-being or dysphoric mood; persistent, unexplained fatigue; and sexual function changes, including decreases in libido, sexual receptivity, and pleasure. Other potential symptoms may be bone loss, decreased muscle strength, and memory or cognition declines.
Since these symptoms can be signs of other diseases, including depression, they are not sufficient for a diagnosis of female androgen insufficiency until other conditions have been ruled out and two other conditions are met:
There is evidence of adequate estrogen, such as normal cycles in premenopausal women or estrogen replacement therapy in postmenopausal women.
The patient has free testosterone values at or below the lowest quartile of the normal range for her reproductive age.
Since sensitive assays and absolute threshold values of androgens have not been established for women, the panel offered the lowest-quartile cutoff as a “clinically useful, albeit arbitrary, criterion for establishing a diagnosis.”
Androgen assays remain a conundrum, the panel acknowledged.
“There was general agreement that the total testosterone assay was not ideal and some concern about the most popular and frequently performed analogue testosterone assay,” panelist Dr. Richard Spark of the department of endocrinology at Beth Israel Deaconess Medical Center, Boston, said in an interview. “The free testosterone by dialysis is perhaps the most accurate but also the most costly and is not performed by most labs.”
Until better options are commercially available, the panel advised clinicians to assess androgen production and androgen availability by obtaining two out of the following three values: total testosterone and sex hormone–binding globulin (SHBG), free testosterone and SHBG, or free testosterone and total testosterone.
“Ideally, testosterone values should be obtained in the morning hours and in the middle third of the menstrual cycle in normally cycling premenopausal women,” the panelists noted.
The Free Testosterone Index (total T/SHBG) correlates well with free testosterone or bioavailable testosterone, but Free Testosterone Index assays “are not well validated for women,” the statement reported.
The most useful measurement of adrenal androgen production in women is dehydroepiandrosterone sulfate (DHEAS), which is reliable and can be used if a clinician suspects an adrenal cause for androgen insufficiency.
The panel said salivary assays and potential biologic markers for androgen insufficiency were not researched well enough to be considered useful diagnostic measures.
Clinicians were cautioned by the panelists to consider other explanations before considering a trial of androgen replacement, including major life stresses or relationship problems, thyroid disease, metabolic or nutritional deficiencies, other causes of chronic fatigue such as Lyme disease, and psychiatric disorders.
An effort should be made to determine and then correct the underlying cause of the deficiency. Commonly, these can include ovarian, adrenal, or hypothalamic-pituitary problems or drug-related causes, but the cause may be idiopathic.
A practical algorithm for initiating therapy in patients who meet diagnostic criteria was published along with the statement (see box ).
No androgen replacement therapy is currently approved in the United States for women, and the panel suggested that physicians offering testosterone supplementation or DHEAS off label should regularly assess their patient's health in light of potential risks, including lipid changes, estrogenic effects, and effects on the mood, voice, and skin.
Dr. Ray Rosen of the Robert Wood Johnson Medical School organized the panel. Dr. Glenn Braunstein of Cedars-Sinai Medical Center in Los Angeles chaired the consensus report committee.
--------------------------------------------------------------------------------
_ Algorithm for Deciding Whether To Initiate Androgen Therapy_
* Does the woman have symptoms consistent with female androgen insufficiency, such as low libido or decreased energy?
If yes, initiate evaluation.
* Is there an alternative explanation or cause for these symptoms—for example, major depression or chronic fatigue syndrome?
If yes, manage as appropriate.
If no, evaluate further.
* Is the woman in an optimum estrogen state?
If yes, continue evaluation.
If no, initiate estrogen replacement.
* Does the woman have laboratory values that are consistent with a diagnosis of androgen insufficiency?
If yes, continue evaluation, including assessment of at least two of three measures of total testosterone, free testosterone, or sex hormone–binding globulin. To meet the diagnosis, androgen values must be in the lowest quartile for women of reproductive age.
If no, consider alternative treatments or a referral.
* Does the woman have a specific treatable cause for androgen insufficiency, such as oral estrogen or oral contraceptive use?
If yes, treat the specific cause (for example, change medications).
If no, consider a trial of androgen replacement therapy.
Source: Fertil. Steril. 77(4):660-65, 2002

 

[wilson6]

I have data from the tranny lit with T administration to otherwise normal women. I'll look at the endocrine workups and comparisons when I get a chance and post what I find.

W6

 

[wilson6]

MS,

Here are the numbers from a 1999 study by Elbers on women to men trannys before ovarian ablation. Normal dose of T is 250 mg/2wk of sus.

Variable, Baseline, and after 12 months of treatment

Test 1.6 nmol/L to 31 nmol/L p<0.001
Estradiol 161 pmol/L to 134 pmol/L not significant
SHBG 58 nmol/L to 25 nmol/L p<0.001
LH 4.3 U/L to 2.2 U/L p<0.05
FSH 4.6 U/L to 3.2 U/L not significant
GH 10.2 ug/L to 4.1 ug/L p<0.001
DHT 0.7 nmol/L to 3.2 nmol/L p<0.001
Insulin no change
Cortisol excretion no change

The elevation in T with the 250 mg/2wk of sus is about 7.5x higher than that in the andro study.

Remember, the andro study is only a single dose evaluation and the andro induced elevations in E1, A and T returned to baseline in 8 - 12 hrs.

W6