Testopel FDA Warning Letter!

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm208007.htm

Whitehead gets what he deserves!

 

Yawn...I'm afraid it still won't stop the bleeding pal. Testim is about to sustain an ass whoopin!

 

Beginning of the end, doors closed by December.

 

That has to be the funniest and also DUMBEST observations I've EVER come across on cafepharma! You aren't playing with a full deck are you?

 

And why is that?

 

Richie Deffenbaugh is there to save the day. He is really brillant. hahahahahahahahahahahah. Maybe Anne Marie will be there next.

 

Hmmmm....I don't know, maybe because Testopel is starting to establish itself as the best TRT on the market???

 

Medicare and insurance companies already "flag" the claims for Testopel because they have a non specific J code. Now with the FDA warning letters, all off label claims will be denied as well as excessive pelllets. More adminstrative issues for Testopel.....and by the way, several attorney generals are looking at Slates pricing and potential fraud.

 

Now this maybe the funniest thing I have ever read on CP.

 

Let the FDA dig deeper. Who knows what theyll find?

 

You really are a dumbass aren't you? Better recheck your sales numbers there pal...you're getting your ass handed to you and it's ONLY going to get worse!

 

I know one thing they won't find...

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2009/ucm149580.htm

 

TRANSMITTED BY FACSIMILE

Robert S. Whitehead, Chief Executive Officer
Slate Pharmaceuticals
318 Blackwell Street, Suite 240
Durham, NC 27701

RE: ANDA #80-911
Testopel® Pellets (testosterone), CIII
MACMIS #18378

WARNING LETTER

Dear Mr. Whitehead:

The Division of Drug Marketing, Advertising, and Communications (DDMAC) of the U.S. Food and Drug Administration (FDA) has reviewed a sales aid (55789) (sales aid) for Testopel® Pellets (testosterone), CIII (Testopel), submitted by Slate Pharmaceuticals (Slate) under cover of Form FDA-2253. Additionally, through its routine monitoring and surveillance program, DDMAC has reviewed web pages1 and a consumer video on the Testopel website (www.testopel.com)2(video). The sales aid, web pages, and video are each misleading for one or more of the following reasons: they promote unapproved uses of Testopel, omit and minimize important risk information associated with Testopel, broaden the indication of Testopel, overstate the efficacy of Testopel, present unsubstantiated superiority claims for Testopel, omit material facts, present misleading convenience claims, present an unapproved dosing regimen for Testopel, and/or present other unsubstantiated claims about Testopel. Therefore, these promotional materials misbrand the drug in violation of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 352(a), (f)(1) & (n); and 321(n), and FDA implementing regulations. See 21 CFR 201.100(c)(1); 201.128; 202.1(e)(3)(i); (e)(5); (e)(6)(i), (ii), (xvii), (xviii); (e)(7)(i) & (viii).

We are extremely concerned by the breadth and scope of violations reflected in your promotional materials. The presentations seen throughout the cited pieces suggesting that Testopel is safer and more effective than has been demonstrated are very problematic from a
public health perspective given the limited indication of the drug and its risk profile.

Furthermore, you failed to submit the web pages and video to FDA under cover of Form FDA-2253, as required by 21 CFR 314.81(b)(3)(i).

Reference is made to the teleconference between DDMAC and Slate on March 16, 2010, during which DDMAC outlined its serious concerns with the pieces referenced above. DDMAC acknowledges that, following the teleconference, Slate committed to comply with DDMAC’s request to immediately cease the use of these materials and to initiate a review of other promotional materials for the same or similar violations. We appreciate this commitment and the steps that Slate has taken thus far to address some of the issues outlined in this letter.

Background

According to its FDA-approved product labeling (PI), Testopel is approved for the following indication:

Males
Androgens are indicated for replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone;

a. Primary hypogonadism (congenital or acquired) – testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchidectomy.

b. Hypogonadotrophic hypogonadism (congenital or acquired) – idiopathic gonadotropin or LHRH deficiency, or pituitary – hypothalamic injury from tumors, trauma, or radiation.

If the above conditions occur prior to puberty, androgen replacement therapy will be needed during the adolescent years for development of secondary sexual characteristics. Prolonged androgen treatment will be required to maintain sexual characteristics in these and other males who develop testosterone deficiency after puberty.

c. Androgens may be used to stimulate puberty in carefully selected males with clearly delayed puberty. These patients usually have a familial pattern of delayed puberty that is not secondary to a pathological disorder; puberty is expected to occur spontaneously at a relatively late date. Brief treatment with conservative doses may occasionally be justified in these patients if they do not respond to psychological support. The potential adverse effect on bone maturation should be discussed with the patient and parents prior to androgen administration. An X-ray of the hand and wrist to determine bone age should be taken every 6 months to assess the effect of treatment on epiphyseal centers . . . .

The use of Testopel is associated with a number of serious risks. Testopel is contraindicated in men with carcinomas of the breast or with known or suspected carcinomas of the prostate, and in pregnant women (as it presents a potential hazard to the fetus). The PI also includes warnings regarding hypercalcemia in patients with breast cancer, development of peliosis hepatitis (which can be a life-threatening or fatal complication) and hepatic neoplasms (including hepatocellular carcinoma) with prolonged use of high doses, increased risk for the development of prostatic carcinoma, edema with or without congestive heart failure in patients with preexisting cardiac, renal or hepatic disease, development of gynecomastia, and acceleration of bone maturation without compensatory gain in linear growth in children and the potential for serious adverse health effects if Testopel is used for purposes not shown to be safe and effective (i.e., for the enhancement of athletic performance).

According to the PRECAUTIONS section of the PI, Testopel implantation has much less flexibility for dosage adjustment than oral administration of or intramuscular injections of oil solutions or aqueous suspensions, requires surgical removal if testosterone should be discontinued, and carries a risk of sloughing out of the skin. In addition, the PI includes precautions regarding frequent or excessive erections of the penis, nausea, vomiting, changes in skin color, ankle swelling, and the need for bone development checks in adolescent patients. The PI also includes precautions regarding drug interactions with oral anticoagulants, oxyphenbutazone, and insulin. Moreover, the PRECAUTIONS section of the PI discusses the need for various laboratory tests, specifically: periodic liver function tests because of associated hepatotoxicity; x-ray examinations of bone age every six months during treatment of prepubertal males; and periodic hemoglobin and hematocrit levels to detect polycythemia in patients who are receiving high doses of androgens.

Furthermore, Testopel includes several adverse reactions including, but not limited to, excessive frequency and duration of penile erections, hirsutism, male pattern of baldness, acne, alterations in liver function tests, suppression of clotting factors II, V, VII, and X, polycythemia, increased or decreased libido, headache, anxiety, depression, generalized parethesia, inflammation and pain at the site of subcutaneous implantation, and anaphylactoid reactions.

According to the DOSAGE AND ADMINISTRATION section of the PI (in pertinent part):

The suggested dosage for androgens varies depending on the age, and diagnosis of the individual patient. Dosage is adjusted according to the patient’s response and the appearance of adverse reactions. The dosage guideline for the testosterone pellets for replacement therapy in androgen-deficient males is 150 mg to 450 mg subcutaneously every 3 to 6 months. Various dosage regimens have been used to induce pubertal changes in hypogonadal males; some experts have advocated lower doses initially, gradually increasing the dose as puberty progresses, with or without a decrease in maintenance levels. Other experts emphasize that higher dosages are needed to induce pubertal changes and lower dosages can be used for maintenance after puberty. The chronological and skeletal ages must be taken into consideration, both in determining the initial dose and in adjusting the dose.

Dosages in delayed puberty generally are in the lower range of that listed above, and for a limited duration, for example, 4 to 6 months.
. . .

Adequate effect of the pellets ordinarily continues for three to four months, sometimes as long as six months.

Promotion of Unapproved Uses

As detailed below, the web pages and video misleadingly suggest several new “intended uses” for Testopel that the drug is not approved to treat.

Web Pages

Several web pages on the Testopel website present the following statements (italicized emphasis in original; bolded emphasis added):

• “Check back for a video of a patient with depression giving his personal perspective on how Testopel® helped him to reclaim his life. . . .” (see “Depression” web page)

• “Check back for a video of a patient with erectile dysfunction giving his personal perspective on how Testopel® helped him to reclaim his life. . . .” (see “Erectile Dysfunction” web page)

• “Check back for a video of a patient with type 2 diabetes giving his personal perspective on how Testopel® helped him to reclaim his life. . . .” (see “Type 2 Diabetes” web page)

• “Check back for a video of a patient with HIV giving his personal perspective on how Testopel® helped him to reclaim his life. . . .” (see “HIV” web page)

• “My doctor suggested testosterone to help with my ED. He explained my options and I choose Testopel® because it sounded the easiest. . . .” (see “Patient Stories” web page)

Additionally, the following claims are presented on the “TESTOPEL® FOR LOW T” web page (emphasis in original):

• “What are the benefits of Testopel® therapy?
. . . .

o Improved mood
o Increased sexual interest
o Restoration of erectile function
o Increased muscle mass
o Increased strength of bones.”

The overall impression conveyed by the above claims misleadingly implies that Testopel can be used to treat the symptoms of depression, erectile dysfunction, type 2 diabetes, HIV, mood disorders, and loss in sexual interest, and that Testopel treatment results in an increase in muscle mass and bone strength. FDA is unaware of any data to support these claims and implications.

Video

The video presents the following statements made by Dr. Abraham Morgentaler, Associate Clinical Professor of Surgery (Urology) at Harvard Medical School, affiliated with Beth Israel Deaconess Medical Center and Founder and Director of Men’s Health Boston, in which he promotes the use of Testopel (emphasis added):

• “I specialize in sexual medicine and in particular work around testosterone.”

• “When we treat them [patients] and we get their levels back to normal -- the guys come back and they say, ‘I feel normal again.’ Their strength may improve, their workouts at the gym may get better, they start chasing their wives around the room a little bit -- they just feel like guys again.”

The totality of these claims misleadingly implies that Testopel can be used to treat sexual dysfunction. FDA is unaware of any data to support these claims.

The video also presents other statements by Dr. Morgentaler as well as a patient’s testimonial about Testopel treatment. Dr. Morgentaler’s statements include the following (emphasis added):

• “I had a patient just the other day who is a golf professional and he found he just wasn’t hitting the ball as far. He had low testosterone.”

• “Their strength may improve, their workouts at the gym may get better . . . .”

The patient’s statements include the following (emphasis added):

• “I was having trouble doing push ups, I couldn’t do more than five to six, and . . . I tried and it really bothered me.”

The totality of these claims misleadingly implies that Testopel has a positive impact on the enhancement of athletic performance of professional (and non-professional) athletes, such that Testopel can improve physical strength in these patients. These claims are especially
concerning because they contradict the Testopel PI; according to the WARNINGS section of the PI, “This drug has not been shown to be safe and effective for the enhancement of athletic performance. Because of the potential risk for serious adverse health effects, this
drug should not be used for such purpose” (emphasis added).

As detailed above, the webpages and video promote unapproved uses for Testopel; as a result, these promotional materials misbrand the drug because the approved PI for Testopel lacks adequate directions for the uses recommended in these promotional materials.

Omission and Minimization of Risk Information

Promotional materials are misleading if they fail to reveal facts that are material in light of the representations made or with respect to the consequences that may result from the use of the drug as recommended or suggested by the materials.

Video

The video omits or minimizes serious risks associated with the use of Testopel. Specifically, the video fails to convey any risks specific to Testopel during the efficacy presentation of the video, which encompasses all but the last ten seconds of the video’s two minute and nine seconds of running time. The only risk information presented is relegated to the end of the video, where it is unlikely to draw the viewer’s attention. Furthermore, this information is presented in small print type in single-spaced paragraph format, with no accompanying audio presentation, and it appears on the screen for less than ten seconds, which does not allow adequate time for viewers to read this information. As such, the presentation of this risk information lacks comparable prominence to the presentation of effectiveness information in the video.

Additionally, although the video presents some of the contraindications associated with Testopel, it completely omits the most serious and important warnings (i.e., hypercalcemia in patients with breast cancer; development of peliosis hepatitis and hepatic neoplasms with prolonged use; increased risk for the development of prostatic carcinoma; edema with or without congestive heart failure in patients with preexisting cardiac, renal, or hepatic disease; development of gynecomastia; and acceleration of bone maturation without compensatory gain in linear growth in children), precautions (i.e., less flexibility for dosage adjustment than oral administration of or intramuscular injections of oil solutions or aqueous suspensions; requires surgical removal if testosterone should be discontinued; carries a risk of sloughing out of skin; frequent or excessive erections of the penis; nausea; vomiting; changes in skin color; ankle swelling; the need for bone development checks in adolescent patients; drug interactions with various drugs; and the need for various laboratory tests), and adverse reactions (i.e., excessive frequency and duration of penile erections; hirsutism; male pattern of baldness; acne; alterations in liver function tests; suppression of certain clotting factors; polycythemia; increased or decreased libido; headache; anxiety; depression; generalized parethesia; inflammation and pain at the site of subcutaneous implantation; and anaphylactoid reactions) for this drug product.
In addition, some of Dr. Morgentaler’s statements about Testopel during the efficacy presentation of the video further minimize the serious risks associated with Testopel. For example, Dr. Morgentaler states the following:

• “The convenience of the pellets can be that it’s a treatment that may last for three to six months for some men. So they [patients] can just come in, get treated, and go about their ways and not have to think about anything else.”

However, according to the PRECAUTIONS, Information for the Patient section of Testopel’s PI, “The physician should instruct patients to report any of the following side effects of androgens: . . . Too frequent or persistent erections of the penis. Any nausea, vomiting, changes in skin color, or ankle swelling.” In light of these risks post-Testopel implantation, it is misleading to imply that upon administration of the drug, patients can “go about their ways and not have to think about anything else.” This statement is especially concerning coming from a healthcare practitioner, considering the potentially serious side effects patients may experience. The video also fails to inform patients that Testopel therapy may need to be discontinued, and the pellets removed, due to complications or side effects, according to the PRECAUTIONS section of the PI.

Sales Aid

Although the back cover of the sales aid presents some of the adverse events associated with Testopel, it completely omits the serious contraindications (i.e., in men with carcinomas of the breast or with known or suspected carcinomas of the prostate and in pregnant women), warnings, precautions, and additional adverse reactions for this drug product (see above). Because the sales aid omits these serious and important risks, it misleadingly suggests that Testopel is safer than has been demonstrated by substantial evidence or substantial clinical experience.

We note that the statement, “PLEASE SEE ACCOMPANYING COMPLETE PRESCRIBING INFORMATION FOR TESTOPEL®” (emphasis in original), is included in green print type at the bottom of the inside right-hand page of the sales aid. However, this is insufficient to mitigate the misleading omission of risk information from this promotional piece.

Web Pages

Several web pages on the Testopel website, including the “TESTOPEL® FOR LOW T” and “Patient Stories” web pages, fail to disclose any risk information for Testopel. We note that the website includes links to “Prescribing Information” and “Important Safety Information” at the very bottom of the web pages in small font, and the “TESTOPEL® FOR LOW T” and “Patient Stories” web pages also include a “Safety Information” link on the right-hand side of the page. However, these links do not mitigate the misleading omission of risk from these pages. For promotional materials to be truthful and non-misleading, they must contain risk information in each part as necessary to qualify any effectiveness or safety claims made in that part (See 21 CFR 202.1(e)(3)(i)).

In addition, the “Important Safety Information” webpage further minimizes the risks associated with Testopel. This web page contains a minimal disclosure of information relating to the contraindications for Testopel but entirely omits the warnings, precautions, and adverse reactions (see above) associated with the use of Testopel.

We are very concerned from a public health perspective about your omission and minimization of risk information throughout the Testopel website, as it serves to severely minimize the risks associated with the use of Testopel.

Broadening of Indication

Promotional materials are misleading if they suggest that a drug is useful in a broader range of conditions or patients than has been demonstrated by substantial evidence or substantial clinical experience. As discussed above, the web pages and video include broad references to possible uses of Testopel (including unapproved uses). The sales aid includes claims that Testopel is “the only FDA approved implantable testosterone pellet” and that Testopel is an “androgen formulation.” The video includes the statement, “Testopel® is indicated for the treatment of conditions associated with a deficiency or absence of endogenous testosterone,” which is presented in small print type under the header “IMPORTANT SAFETY INFORMATION” during the last ten seconds of the video. However, the web pages, video, and sales aid all fail to disclose the full indication for Testopel, including the important limitations to the indication. As a result, these promotional materials suggest, among other things, that Testopel is approved to treat all conditions or patients for testosterone replacement. However, Testopel is only indicated for replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone with specific material limitations (see Background section above).

Regarding the video, we note that it includes the statement, “See Accompanying Full Prescribing Information” at the end of the “IMPORTANT SAFETY INFORMATION” section. In addition, we note the sales aid includes the statement, “PLEASE SEE ACCOMPANYING COMPLETE PRESCRIBING INFORMATION FOR TESTOPEL®” (emphasis in original) in green print type at the bottom of the inside right-hand page of the sales aid. However, these statements do not mitigate the misleading omission of Testopel’s full indication from these pieces, including important limitations.

Overstatement of Efficacy

Promotional materials are misleading if they represent or suggest that a drug is more effective than has been demonstrated by substantial evidence or substantial clinical experience.

Sales Aid

The sales aid for Testopel presents the headline claim, “RECLAIM YOUR LIFE™,” (emphasis in original) in conjunction with three graphic images of a man jogging, a man playing with a child, and a man kissing a woman.

Web Pages

The “Depression,” “Erectile Dysfunction,” “Type 2 Diabetes,” and “HIV” web pages present the following statements (emphasis added):

• “Check back for a video of a patient with depression [erectile dysfunction, type 2 diabetes, or HIV] giving his personal perspective on how Testopel® helped him to reclaim his life.”

In addition, the “Patient Stories” web page includes the following testimonial (italicized emphasis in original; bolded emphasis added):

• “My son suffers from Klinefelter’s syndrome. Like any 14 year old, he just want to do the same things as his friends – to be “normal.” Rubbing on his medication every day was always a problem and his levels were all over the place. Testopel® has been a life saver for him and our family. For mothers of Klinefelter’s sons everywhere, thank you Slate!”

Video

Furthermore, the video presents statements by Dr. Morgentaler and a patient on Testopel treatment. Dr. Morgentaler’s statements include the following (emphasis added):

• “When we treat them [patients] and get their levels back to normal -- the guys come back and say, ‘I feel normal again.’”

The patient’s statements in the video include the following (emphasis added):

• “My symptoms were really slowing down -- I was feeling old.”
• “Before this my brain was slowing down, and I didn’t want to do things, you know. But now I got a lot of get up and go, and I want to do . . . things all the time . . . .”

The above claims in the sales aid, web pages, and video imply that an outcome of treatment with Testopel is the ability for patients to resume their “normal” activities and lifestyle (i.e., to reclaim their lives). FDA is not aware of any studies that measured these outcomes or any other evidence to support such effects of Testopel treatment. If you have such evidence, please submit it to FDA for our review. We further note that Testopel treatment is associated with serious warnings, such as prostatic hypertrophy and prostatic carcinoma and edema with or without congestive heart failure (see Background section above), any of which can negatively affect a patient’s everyday activities or lifestyle.

Unsubstantiated Superiority Claims/Overstatement of Efficacy

Promotional materials are misleading if they contain a drug comparison that represents or suggests that a drug is safer or more effective than another drug, when this has not been demonstrated by substantial evidence or substantial clinical experience. Furthermore, promotional materials are misleading if they contain representations that the drug is better or more effective than has been demonstrated by substantial evidence or substantial clinical experience.

Sales Aid

The sales aid includes the following claims that compare the efficacy of Testopel to other testosterone treatments (emphasis in original):

• “ONLY TESTOSTERONE PELLETS YIELD SERUM TESTOSTERONE LEVELS WITHIN NORMAL RANGE FOR SEVERAL MONTHS”3 (inside page left-hand side)

o “By day 2 post pellet insertion all patients had reached a serum T level plateau.”3
o “Testosterone levels remained above the lower limit of normal (10 nmol/l) for ~6 months.”3
o “Author’s Conclusion: ‘T-pellets are the androgen formulation with the longest biological action and strongest pharmacodynamic efficacy in terms of gonadotrophin suppression. The pharmacokinetic features are advantageous compared to other T preparations and the patient acceptance is high.’”

The above claims are presented in conjunction with a graph titled, “Testosterone Pellets Deliver Months of Serum T Levels Within Normal Range” (emphasis in original), which displays levels of testosterone (nmol/L) over time (days). These claims and presentation are misleading because they imply that Testopel is clinically superior to other testosterone formulations because it is the only formulation that delivers testosterone levels within normal range for approximately six months. The Jockenhövel, et al. reference cited5 does not constitute substantial evidence or substantial clinical experience to support this presentation. Generally, superiority claims must be supported by adequate and well-controlled head-to-head clinical trials comparing appropriate doses and dose regimens of your drug and the comparator drug. The Jockenhövel, et al. study, however, was a single-dose, open-label, non-randomized pharmacokinetic study. Additionally, the study did not examine Testopel, but instead used a testosterone implant that is not approved in the United States (200 mg subdermal testosterone implants that are manufactured by Organon in Oss, the Netherlands). As such, it does not constitute substantial evidence to support the presentation in the sales aid.

Patient Preference Claims

Sales Aid
The sales aid includes the following claims that compare patient preference for Testopel to all other testosterone products (emphasis in original):

• “92% of men choose to continue with Testopel® rather than switch back to their prior testosterone therapy” (front cover)
• “9 OF 10 MEN PREFER TESTOSTERONE PELLET THERAPY OVER THEIR PREVIOUS FORM OF TREATMENT”4 (inside page right-hand side)

o “Multiple studies demonstrate that men are so highly satisfied with testosterone pellet treatment that they choose to continue receiving pellets rather than returning to their previous form of therapy”4

These claims are misleading because they imply that the vast majority of patients prefer Testopel to all other forms of testosterone therapy that are currently on the market, when this has not been supported by substantial evidence or substantial clinical experience. The Seftel, et al. article cited in the sales aid includes references to the Jockenhövel, et al., Handelsman, Mackey, et al.,5 and Handelsman, Conway, et al.6 articles—all of which do not constitute substantial evidence or substantial clinical experience to support these claims. Generally, as stated above, superiority claims must be supported by adequate and wel-lcontrolled head-to-head clinical trials comparing appropriate doses and dose regimens of your drug and the comparator drug. These references do not describe adequate and well-controlled head-to-head studies that evaluated patient preference for patients on Testopel compared to their previous treatments. In fact, these studies did not examine Testopel, but instead used testosterone pellets and dosage strengths that are not approved in the United States (20 mg, 100 mg, and 200 mg testosterone implants that are manufactured by Organon in Oss, the Netherlands). Additionally, the studies were published in 1996, 1997, and 1990, respectively, and, therefore, did not evaluate patient preference of newer formulations of testosterone in the current marketplace.

Furthermore, patient preference is a broad concept that encompasses multiple aspects of patient experiences, such as convenience, ease of use, dosing, dosage form, all aspects of efficacy, and adverse events. The cited references were not designed to evaluate such
patient experiences.

Omission of Material Facts/Unsubstantiated Convenience Claims

Video

The video presents the following statements made by Dr. Morgentaler about the superior convenience of Testopel compared to other testosterone formulations:

• “One of the advantages of that treatment is the guy doesn’t need to treat himself everyday with a gel or a patch, and he doesn’t need to get frequent injections.”

• “The convenience of the pellets can be that it’s a treatment that may last for three to six months for some men. So they can just come in, get treated, and go about their ways and not have to think about anything else.”

Web Pages

Similarly, the “Patient Stories” web page includes the following statements (italicized emphasis in original; bolded emphasis added):

• “Worrying about my testosterone gel getting onto my wife or young kids was a problem. My wife was frustrated during our hectic mornings when I couldn’t help by holding the baby. Testopel® just simplifies things. She’s happy, I’m happy, the kids are happy.”

• “. . . I choose Testopel® because it sounded the easiest . . . Still I was nervous for my first procedure. It was so simple. He was done before I knew it.”

The “TESTOPEL® FOR LOW T” web page includes the following claim (emphasis added):

• “Unlike other testosterone medications, Testopel® is administered once every 3-6 months in a fast and simple in-office procedure.”

Sales Aid

The sales aid includes the following claim (emphasis added):

• “Testopel® is administered in an easy office based procedure that takes 10 minutes or less.” (front cover)

In addition, the sales aid includes the claim, “TESTOPEL® ELIMINATES MANY OF THE HASSLES ASSOCIATED WITH GEL THERAPY,” in conjunction with a table that presents the following statements (emphasis in original):

• “Daily Application of Therapy Required”;
• “Monthly Trip to Pharmacy”;
• “Potential for Transfer of Medication to Others”; and
• “Wait 5-6 hours Post Daily Application to Shower, Swim, or Perspire.”

The responses to each of these statements are “NO” for Testopel and “YES” for gel therapy (emphasis in original).

The overall impression of the above claims and presentations in the video, web pages, and sales aid is that Testopel is more convenient than gel therapy, a patch, or injectable treatments because Testopel eliminates many of the hassles or inconveniences associated with these other treatments. While we acknowledge that Testopel is administered differently than other therapies, FDA is not aware of any evidence that Testopel is more convenient than testosterone gel, patch, or injectable treatments for this patient population. While the sales aid, video, and web pages selectively present attributes that are the most favorable for Testopel compared to other therapies, they omit material information about other attributes of Testopel therapy, including serious risks, that could impede its convenience and are highly relevant to any decision about whether to prescribe or use Testopel or other treatments. For example, according to its PI, Testopel implantation requires a surgical procedure and must be implanted every three to six months, possesses less flexibility for dosage adjustment than oral administration or intramuscular injection of oil solutions or aqueous suspensions (i.e., gel therapy), requires surgical removal if Testopel should be discontinued, carries a risk of sloughing out of the skin, and may cause inflammation and pain at the site of implantation.

Thus, we are not aware of evidence to support the implication that Testopel is more convenient than other treatment options. If you have evidence to support such a claim, please submit it to FDA for review.

Moreover, the above claims suggest that Testopel treatment is an easy office procedure that takes ten minutes or less. We are not aware of any evidence to support the assertion that the administration of Testopel is “easy,” “fast,” or “simple” from either the healthcare provider’s or patient’s perspective. In fact, these claims are particularly troubling considering the factors that must be taken into account for the implantation process for Testopel (e.g., making an incision, the use of local anesthesia, whether the pellets are to be implanted in separate tracks, and the distance from the insertion site to the final location of the pellets), and the adverse events that could occur at the implantation site, such as “nflammation and pain at the site of the subcutaneous implantation of testosterone containing pellets,” according to Testopel’s PI.

Misleading Comparative Claims/Promotion of Unapproved Dosing Regimen

Sales Aid

The sales aid presents the following claims (emphasis in original):

• “TESTOPEL® IS HALF THE PRICE OF GEL THERAPY

o When 8 pellets are administered, TESTOPEL® is half the cost of conventional testosterone gel therapy.”

The above claims are presented in conjunction with a bar graph showing the average wholesale price (AWP) for 4.5 months of therapy, comparing eight pellets of Testopel ($700) to Testim® ($1,401) and AndroGel® ($1,515). The prices represented in the bar graph
misleadingly imply that all costs associated with Testopel and gel therapy have been considered. However, the presentation does not disclose all costs involved with Testopel compared to gel therapy (e.g., healthcare provider office visits, surgical procedures to implant Testopel, management of adverse events, dosage adjustments, and laboratory monitoring).Thus, the claim that Testopel is half the cost of gel therapy is misleading.

Furthermore, these claims and presentation imply an unapproved dosing regimen for Testopel—i.e., that eight pellets of Testopel is the usual dosage for the drug’s indicated use. However, according to the DOSAGE AND ADMINISTRATION section of Testopel’s PI, the dosage guideline for replacement therapy in androgen-deficient males is 150 mg to 450 mg (two to six 75 mg pellets) every three to six months. We are not aware of any data to support a usual dosage of eight pellets for Testopel’s approved indication.

Unsubstantiated Claims

The “TESTOPEL® FOR LOW T” web page includes the following claims (emphasis added):

• “Other than the initial stick of a needle used to numb the insertion area, Testopel® insertion is pain-free.”

• “Once implanted, most men have no awareness that the pellets are there.”

The above claims misleadingly suggest that the insertion of Testopel is “pain-free” (other than the initial needle stick) and that once Testopel is implanted, most patients will not feel the pellets. FDA is unaware of any evidence to support that the administration of Testopel is “pain-free” or that once administered, most men are not aware that the pellets are implanted. These claims are further concerning in light of the adverse reactions associated with Testopel discussed above, such as inflammation and pain at the site of implantation.

Failure to Submit Under Form FDA-2253

Web Pages and Video

FDA regulations require companies to submit specimens of any labeling or advertising devised for promotion of the drug product at the time of initial dissemination of the labeling and at the time of initial publication of the advertisement for a prescription drug product. Each submission is required to be accompanied by a complete transmittal Form FDA-2253 (Transmittal of Advertisements and Promotional Labeling for Drugs for Human Use) and is required to include a copy of the product’s current professional labeling. A copy of the web pages and the video were not submitted to FDA under cover of Form FDA-2253 as required by CFR 314.81(b)(3)(i).

Conclusion and Requested Action

For the reasons discussed above, the sales aid, web pages, and video misbrand Testopel in violation of the Act, 21 U.S.C. 352(a), (f)(1) & (n); and 321(n), and FDA’s implementing regulations. See 21 CFR 201.100(c)(1); 201.128; 202.1(e)(3)(i); (e)(5); (e)(6)(i), (ii), (xvii), (xviii); (e)(7)(i) & (viii). Furthermore, you failed to submit the web pages and video to FDA under cover of Form FDA-2253, as required by 21 CFR 314.81(b)(3)(i).

DDMAC requests that Slate submit a written response to this letter on or before April 7, 2010, with a complete listing of the promotional materials (with the 2253 submission date) that you have discontinued for Testopel as a result of the March 16, 2010 teleconference and this letter. Because the violations described above are serious, we request, further, that your submission include a comprehensive plan of action to disseminate truthful, non-misleading, and complete corrective messages about the issues discussed in this letter to the audience(s) that received the violative promotional materials.

Please direct your response to me at the Food and Drug Administration, Center for Drug Evaluation and Research, Division of Drug Marketing, Advertising, and Communications, 5901-B Ammendale Road, Beltsville, MD 20705-1266, facsimile at (301) 847-8444. In all future correspondence regarding this matter, please refer to MACMIS# 18378 in addition to the NDA number. We remind you that only written communications are considered official.

The violations discussed in this letter do not necessarily constitute an exhaustive list. It is your responsibility to ensure that your promotional materials for Testopel comply with each applicable requirement of the Act and FDA implementing regulations.

Failure to correct the violations discussed above may result in FDA regulatory action, including seizure or injunction, without further notice.

Sincerely,

{See appended electronic signature page}

Thomas Abrams, R.Ph., M.B.A.
Director
Division of Drug Marketing,
Advertising and Communications

 

Happy Aniversary

FDA NEWS RELEASE
FOR IMMEDIATE RELEASE
May 7, 2009
Media Inquiries:
Rita Chappelle, 301-796-4672
Consumer Inquiries:
888-INFO-FDA



Testosterone Gel Safety Concerns Prompt FDA to Require Label Changes, Medication Guide

The U.S. Food and Drug Administration today announced that it is requiring manufacturers of two prescription topical testosterone gel products, AndroGel 1% and Testim 1%, to include a boxed warning on the products’ labels. The agency is requiring this action after receiving reports of adverse effects in children who were inadvertently exposed to testosterone through contact with another person being treated with these products (secondary exposure).

The gels are approved for use in men who either no longer produce testosterone or produce it in very low amounts. Both products are applied once daily, to the shoulders or upper arms. Only AndroGel 1% is approved for application to the abdomen. Precautions in the current labels instruct users to wash their hands after using the product and to cover the treated skin with clothing.

“These drugs are approved for an important medical need, but can have serious, unintended side effects if not used properly,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “We must ensure that the adults using them are well-informed about the precautions needed to protect children from secondary exposure.”

In 2007, 1.4 million prescriptions for AndroGel—the most commonly dispensed gel form of testosterone—were dispensed by U.S. retail pharmacies. Approximately 25,000 of those were dispensed for off-label use in women. During the same period, some 370,000 prescriptions were dispensed for Testim, according to data from SDI: Vector One National.

Despite the currently labeled precautions, as of Dec. 1, 2008, the FDA has received reports of eight cases of secondary exposure to testosterone in children ranging in age from nine months to five years. Since that time, additional reports of secondary exposure have been received by the agency and are presently under review.

Of the fully reviewed cases, adverse events reported in these children included inappropriate enlargement of the genitalia (penis or clitoris), premature development of pubic hair, advanced bone age, increased libido, and aggressive behavior.

In most cases, the signs and symptoms regressed when the child no longer was exposed to the product. However, in a few cases, enlarged genitalia did not fully return to age-appropriate size and bone age remained modestly greater than the child’s chronological age.

In some cases, children had to undergo invasive diagnostic procedures and, in at least one case, a child was hospitalized and underwent surgery due to a delay in recognizing the underlying cause of the signs and symptoms.

Signs of inappropriate virilization (development of male secondary sexual characteristics) in children and the possibility of secondary testosterone exposure should be brought to a health care provider’s attention.

In most of the cases, users of these products failed to follow appropriate use instructions, resulting in direct contact between treated skin and the child.
The required label changes will provide additional information about the risk of secondary exposure and the steps that should be taken to reduce this risk. The FDA also is requiring that the manufacturers of these products develop a Medication Guide as part of a Risk Evaluation and Mitigation Strategy to ensure that the benefits of these products continue to outweigh their potential risks.

The FDA recommends the following precautions be taken to minimize the potential for secondary exposure:

Adults who use testosterone gels should wash their hands with soap and warm water after every application;
Adults should cover the application site with clothing once the gel has dried;
Adults should wash the application site thoroughly with soap and warm water prior to any situation where skin-to-skin contact with another person is anticipated;
Children and women should avoid contact with testosterone application sites on the skin of men who use these products; and
Adults should note that use of any similar, but unapproved, products from the marketplace — including the Internet — that can result in the same serious adverse effects should be avoided.
Health care professionals and consumers may report serious adverse events (side effects) or product quality problems with the use of these gels to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail, fax or phone.

Online1
Regular Mail: use postage-paid FDA form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
Fax: (800) FDA-0178
Phone: (800) FDA-1088
AndroGel 1% is manufactured by Marietta, Ga.-based Solvay Pharmaceuticals. Testim 1% is made by Auxilium Pharmaceuticals, Malvern, Pa.


For more information:
Information on FDA's Drug Safety Initiative
Information on FDA-approved drugs2
#


RSS Feed for FDA News Releases3 [what is RSS?4]


-

 

The difference between these two posts is that the FDA's testosterone gel warning was related to the potential for transference, did nothing to affect sales, and had nothing to do with culpability on the part of the manufacturer. However, the FDAs Warning letter to Slate has everything to do with the company's culpability.

So...one FDA action led to absolutely nothing, and the other could be the first step in the withdrawal of Testopel from the market.

Big difference!

 

Nice try. "FDA action led to absolutly nothing" tell that to those poor children that continue to be abused by your sticky smelly goop. Good luck explaining to a jury about your lack of "culpability"

COMMENTARY
Transfer of Topical Testosterone Preparations to Children
or Spousesjsm_1478 2649..2652
Tyler Lewis,* and Irwin Goldstein, MD*†
*Sexual Medicine, Alvarado Hospital, San Diego, CA, USA; †Department of Surgery, University of California at San
Diego, San Diego, CA, USA
DOI: 10.1111/j.1743-6109.2009.01478.x
Testosterone gel (1%) products have been
approved by government regulation agencies
for use in men with testosterone deficiency
syndrome since 2000 and 2003 [1,2]. Efficacy
studies have shown topical testosterone preparations
to improve such outcomes as sexual function,
libido, mood, muscle mass, muscle strength,
and energy [3–7]. Topical 1% testosterone gel is
also associated with eugonadal testosterone
values, unlike the peaks and troughs related to
intramuscular testosterone enanthate or cypionate
injections [1,2]. Topical 1% testosterone
gel is further associated with fewer reactions at
the application site compared to testosterone
patch therapy [1,2]. As a result of the benefits of
topical testosterone gel over intramuscular and
patch testosterone alternatives, topical gel products
have become a widely utilized therapeutic
option for men with testosterone deficiency syndrome,
especially those with hypogonadism and
sexual health concerns.
On May 6, 2009, however, the Food and Drug
Administration (FDA) notified health care professionals
that prescription testosterone gel products
will be required to include a boxed warning on
product labels after the FDA received a number of
reports of adverse events in children and spouses.
To date, reports concerning drug transfer to children
and spouses have been primarily published in
endocrinology and pediatric journals, with only
two reports in The Journal of Sexual Medicine published
in 2005 [8,9]. Patients with sexual health
complaints frequently have low levels of testosterone,
and as a result, sexual medicine health care
providers are large prescribers of topical testosterone
replacement products [10–16], including
approved testosterone gels and non-approved testosterone
creams, ointments, and sprays. It is
important that sexual medicine health care providers
be familiar with the issues of hyperandrogenism
in women and virilization in young
children secondary to drug transfer from topical
testosterone preparations.
The case of a 2-year-old boy who came into skin
contact with testosterone gel presents some of the
negative implications associated with exposure to
topical testosterone [17]. The boy was taken to his
pediatrician because of pubic hair growth. It was
discovered that this pubic hair growth was not
accompanied by testicular enlargement, acne, or
body odor. Further investigation revealed that the
pubic hair growth had been present for 4 months,
and neither parent had a history of precocious
sexual development. However, it was discovered
that the child’s father had been using testosterone
cream for the previous 12 months to treat his testosterone
deficiency syndrome. The child’s father
applied the cream to his forearms nightly, but did
not usually have contact with his son until the
following morning. When the father ceased use of
the testosterone cream, the boy demonstrated no
progression of puberty [17].
Similar results were found among other exposed
children. An 18-month-old girl was taken to her
doctor following pubic hair growth and clitoromegaly
[18]. Her stepfather applied testosterone
cream to his thighs and then allowed the child to sit
on his lap. When the girl was examined, it was
revealed that her bone age was 3 years, while her
chronological age was 18 months. Her serum testosterone
level was measured at 390 ng/dL when the
desired measurement for children is less than
2649
© 2009 International Society for Sexual Medicine J Sex Med 2009;6:2649–2652
10 ng/dL. The child’s mother began applying the
cream to the stepfather’s back using rubber gloves,
and subsequent measurements revealed that the
child’s testosterone level returned to less than
10 ng/dL. Similarly, a 5-year-old girl presented
with marked pubic hair growth and acne that had
been present for 9 months. For bodybuilding, her
father used a spray containing testosterone and
often allowed the child to sleep in his bed. When
the father stopped using the product, the puberty
progression displayed in the child ceased [18].
Long-term effects of childhood exposure to
topically applied testosterone cream result in the
onset of puberty-related symptoms [19]. The most
common symptoms include pubic hair growth,
acne, and an increase in skeletal size so that the
child’s physical age begins to differ significantly
from the child’s chronological age. While testosterone
exposure has been shown to cause virilization
in children who have long-term exposure,
there has been stabilization or decrease of symptoms
following the cessation of testosterone exposure
[19]. Overall, the literature suggests that
the prognosis is very good for children who are no
longer exposed to topically applied forms of
testosterone.
However, in the Pediatric Advisory Panel notes,
the following statement appears: “Despite the
current FDA labeling, FDA continues to receive
these reports and the reports describe serious outcomes
including surgical intervention, advance
bone age and potential for lifelong consequences
secondary to unintended exposure to testosterone.
The review suggests that some of the sequelae
such as sexual organ enlargement may be irreversible
[20].
Topical testosterone use can also have negative
implications for female partners, particularly postmenopausal
women, who are more likely to experience
symptoms of testosterone excess than male
partners. For example, a 63-year-old female professional
singer began to notice a deepening and
coarsening of her voice followed later by balding
toward the front of her cranium and clitoromegaly
[21]. She also noticed increased muscle mass and
hair growth on her chin and stomach area, as well
as the need to shave more often. Further examination
revealed that her husband had been using a
topical testosterone cream for 2 years. While he
reported that he applied the cream to his shoulders
and immediately washed his hands, it was later
discovered that the woman was exposed by sharing
the washcloth the husband used to wipe his hands
after applying the cream. The woman saw marked
improvement when her husband switched to a testosterone
patch. He later switched back to the
cream, but the couple refrained from sharing a
washcloth, and the woman’s symptoms remained
stable [21].
A similar case study involved a 31-year-old
woman who showed signs of progressive hirsutism
[22]. She had no evidence of clitoromegaly, baldness,
or deepening of the voice. Her testosterone
levels exceeded the normal range. She was indirectly
exposed to testosterone from her partner
using a topical testosterone cream for hypogonadism
after treatment for testicular cancer. When
the couple took steps to reduce exposure, the
patient continued to have elevated levels of testosterone,
but once her partner switched to an
injectable form of testosterone her levels returned
to normal [22].
Testosterone levels in women and children are
typically less than 5–10% the testosterone levels
found in men; therefore, even small amounts of
exposure to testosterone by skin-to-skin transfer
can have immediate and negative implications for
these populations [22]. While not common, indirect
exposure to topically applied testosterone
preparations must be prevented in order to protect
women and children.
While the numbers of documented cases of
children and female partners indirectly exposed to
topically applied testosterone gels or creams are
small [22], there are likely many more undocumented
cases. We recently performed an informal
survey on an e-mail Listserv of specialists in sexual
medicine and were surprised by the response. In
just one effort on the Listserv, five separate cases of
testosterone transfer to children or partners were
reported, none of which had previously been
announced to authorities or documented in peer
review literature. When each author was encouraged
to publish the data, three were hesitant to be
involved despite assurances of anonymity because
of medical–legal concerns.
While researching this commentary, we
accessed a public document from the Department
of Health and Human Services, Public Health
Service, FDA, Center for Drug Evaluation and
Research, Office of Surveillance and Epidemiology
dated February 9, 2009 [20]. This review
summarized pediatric adverse event reports
associated with a government-approved 1% testosterone
gel performed in accordance with the
Best Pharmaceuticals for Children Act or Pediatric
Research Equity Act. After nine cases describing
events associated with indirect exposure of test-
2650 Lewis and Goldstein
J Sex Med 2009;6:2649–2652
osterone gel to a child were reported, the sponsor
reported 17 additional pediatric cases including
one case of clitoromegaly requiring surgery and
more than 100 adult cases of indirect exposure
associated with testosterone gel [20].
In summary, this commentary highlights the
growing evidence for testosterone transfer to children
and partners from use of topical testosterone
preparations. There is a need for sexual medicine
health care providers to emphasize to their
patients using topical testosterone as treatment for
testosterone deficiency syndrome to utilize the
suggested FDA warnings and precautions, or to
offer non-topical alternative routes of testosterone
administration.
The following are some FDA warnings and precautions
concerning potential transfer of topical
testosterone to another person.
1. Patients should wash their hands immediately
with soap and water after application of testosterone
gel.
2. Patients should cover the application site(s)
with clothing after the gel has dried (e.g., a
shirt). In the event that unwashed or unclothed
skin to which topical testosterone has been
applied does come in direct contact with the
skin of another person, the general area of
contact on the other person should be washed
with soap and water as soon as possible. In vitro
studies show that residual testosterone is
removed from the skin surface by washing with
soap and water.
3. Women and children should avoid skin contact
with topical testosterone application sites in
men. Changes in body hair distribution, significant
increase in acne, or other signs of virilization
should be brought to the attention of a
physician. Topical testosterone may cause fetal
harm in a pregnant woman because of virilization
of a female fetus.
Conflict of Interest: None declared.
References
1 Wang C, Swerdloff RS, Iranmanesh A, Dobs A,
Snyder PJ, Cunningham G, Matsumoto AM,Weber
T, Berman N, Testosterone Gel Study Group.
Transdermal testosterone gel improves sexual function,
mood, muscle strength, and body composition
parameters in hypogonadal men. J Clin Endocrinol
Metab 2000;85:2839–53.
2 McNicholas TA, Dean JD, Mulder H, Carnegie C,
Jones NA. A novel testosterone gel formulation
normalizes androgen levels in hypogonadal men,
with improvements in body composition and sexual
function. BJU Int 2003;91:69–74.
3 Guay AT, Smith TM, Offutt LA. Absorption of
testosterone gel 1% (testim) from three different
application sites. J Sex Med 2009; doi: 10.1111/
j.1743-6109.2009.01366.x.
4 Reyes-Vallejo L, Lazarou S, Morgentaler A. Subjective
sexual response to testosterone replacement
therapy based on initial serum levels of total testosterone.
J Sex Med 2007;4:1757–62.
5 Amano T, Imao T, Takemae K, Iwamoto T,
Yamakawa K, Baba K, Nakanome M, Sugimori H,
Tanaka T, Yoshida K, Katabami T, Tanaka M.
Profile of serum testosterone levels after application
of testosterone ointment (glowmin) and its clinical
efficacy in late-onset hypogonadism patients. J Sex
Med 2008;5:1727–36.
6 Khera M. Androgens and erectile function: A case
for early androgen use in postprostatectomy
hypogonadal men. J Sex Med 2009;6:S234–8.
7 Khera M, Grober ED, Najari B, Colen JS,
Mohamed O, Lamb DJ, Lipshultz LI. Testosterone
replacement therapy following radical prostatectomy.
J Sex Med 2009;6:1165–70.
8 Spielberg TE. Abnormal testosterone levels in partners
of patients using testosterone gels. J Sex Med
2005;2:278.
9 Mazer N, Fisher D, Fischer J, Cosgrove M, Bell D,
Eilers B. Transfer of transdermally applied testosterone
to clothing: A comparison of a testosterone
patch versus a testosterone gel. J Sex Med 2005;2:
227–34.
10 Hackett G, Kell P, Ralph D, Dean J, Price D,
Speakman M, Wylie K. British Society for Sexual
Medicine. British Society for Sexual Medicine
guidelines on the management of erectile dysfunction.
J Sex Med 2008;5:1841–65.
11 O’Connor DB, Corona G, Forti G, Tajar A, Lee
DM, Finn JD, Bartfai G, Boonen S, Casanueva FF,
Giwercman A, Huhtaniemi IT, Kula K, O’Neill
TW, Pendleton N, Punab M, Silman AJ, Vanderschueren
D, Wu FC. Assessment of sexual health in
aging men in Europe: Development and validation
of the European Male Ageing Study sexual function
questionnaire. J Sex Med 2008;5:1374–85.
12 Corona G, Jannini EA, Mannucci E, Fisher AD,
Lotti F, Petrone L, Balercia G, Bandini E, Chiarini
V, Forti G, Maggi M. Different testosterone levels
are associated with ejaculatory dysfunction. J Sex
Med 2008;5:1991–8.
13 Corona G, Mannucci E, Fisher AD, Lotti F,
Petrone L, Balercia G, Bandini E, Forti G, Maggi
M. Low levels of androgens in men with erectile
dysfunction and obesity. J Sex Med 2008;5:2454–63.
14 Maggi M, Schulman C, Quinton R, Langham S,
Uhl-Hochgraeber K. The burden of testosterone
deficiency syndrome in adult men: Economic
Topical Testosterone Transfer 2651
J Sex Med 2009;6:2649–2652
and quality-of-life impact. J Sex Med 2007;4:1056–
69.
15 Guay A, Jacobson J. The relationship between testosterone
levels, the metabolic syndrome (by two
criteria), and insulin resistance in a population of
men with organic erectile dysfunction. J Sex Med
2007;4:1046–55.
16 Corona G, Mannucci E, Petrone L, Balercia G,
Paggi F, Fisher AD, Lotti F, Chiarini V, Fedele D,
Forti G, Maggi M. NCEP-ATPIII-defined metabolic
syndrome, type 2 diabetes mellitus, and prevalence
of hypogonadism in male patients with sexual
dysfunction. J Sex Med 2007;4:1038–45.
17 Stephen MD, Jehaimi CT, Brosnan PG, Yafi M.
Sexual precocity in a 2-year old boy caused by
indirect exposure to testosterone cream. Endocr
Pract 2008;14:1027–30.
18 Kunz GJ, Klein KO, Clemons RD, Gottschalk ME,
Jones KL. Virilization of young children after
topical androgen use by their parents. Pediatrics
2004;114:282–7.
19 Bhowlick SK, Ricke T, Rettig KR. Sexual precocity
in a 16-month old boy induced by indirect topical
exposure to testosterone. Clin Ped 2007;46:540–
3.
20 FDA Center for Drug Evaluation and Research.
Androgel (testosterone) OSE safety review. 2009.
Available at: http://www.fda.gov/downloads/
AdvisoryCommittees/CommitteesMeeting
Materials/PediatricAdvisoryCommittee/
UCM166660.pdf (accessed July 12, 2009).
21 Merhi ZO, Santoro N. Postmenopausal virilization
after spousal use of topical androgens. Fertil Steril
2007;87:976–8.
22 de Ronde W. Hyperandrogenism after transfer of
topical testosterone gel: Case report and review of
published and unpublished studies. Hum Reprod
2009;24:425–8.
2652 Lewis and Goldstein
J Sex

 

I'm curious to know who you are. Is this Bob? I assume you work for Slate.

 

No...I'm your conscience and I work inside your head. Now go to bed.. you're tired and stupid

 

What does my conscience have to do with testosterone gel transference?

I won't waste my breath insulting you. Just trying to have an intelligent debate with someone from Slate.

 

Yes, but Slate has morally bankrupt leadership. Bob W is a low life, just ask Jessica and Robin.